Population frequency¶

A population frequency filter is applied to prevent common variants being prioritised. For a variant to pass this filter, the population frequency cannot exceed any of the thresholds applied for the mode of inheritance being considered. Variants for which there is no allele population provided in the particular data set and population combination are considered zero.

The datasets used for allele frequency filtering are:

gnomAD genomes v3.1.2
gnomAD exomes v2.1.1
Genomics England allele frequencies

The current GRCh38 allele frequency thresholds for the following populations are as follows:

Dataset tag	Population	Dataset size (individuals)	Dominant inherited disease	Recessive inherited disease	Mitochondrial genome inherited disease
GNOMAD_EXOMES	AMR	17,296	0.001	0.01
GNOMAD_EXOMES	ASJ	5,040	0.001	0.01	n/a
GNOMAD_EXOMES	EAS	9,157	0.001	0.01	n/a
GNOMAD_EXOMES	FIN	10,824	0.001	0.01	n/a
GNOMAD_EXOMES	NFE	56,855	0.001	0.01	n/a
GNOMAD_EXOMES	SAS	15,308	0.001	0.01	n/a
GNOMAD_GENOMES	AFR	20,744	0.001	0.01	n/a
GNOMAD_GENOMES	AMI	456	0.100	0.10	n/a
GNOMAD_GENOMES	AMR	7,647	0.001	0.01	n/a
GNOMAD_GENOMES	ASJ	1,736	0.003	0.01	n/a
GNOMAD_GENOMES	EAS	2,604	0.002	0.01	n/a
GNOMAD_GENOMES	FIN	5,316	0.001	0.01	n/a
GNOMAD_GENOMES	MID	158	0.100	0.10	n/a
GNOMAD_GENOMES	NFE	34,029	0.001	0.01	n/a
GNOMAD_GENOMES	SAS	2,419	0.002	0.01
GEL_aggCOVID_DRAGENv4.0-20230921 (internal ref: 20230921-aggDRAGENv4.0_COVID_v1.1-AFgt0)	Genomics England custom frequencies	5,415	0.001	0.01	0.001

Note

gnomAD frequencies are extracted from gnomAD genomes v3.1.2 and gnomAD exomes v2.1.1. Variants present in gnomAD can receive flags that impact the variant's annotation and/or confidence - further information on possible flags is available through the gnomAD website. Variant frequencies in gnomAD are considered in the Rare Disease tiering pipeline regardless of the flags present.

Note

Several populations considered during variant tiering in earlier versions of the variant tiering pipeline are no longer considered, including: UK10K, 1000 Genomes Phase 3 and DiscovEHR