Variant chr1-46406041-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001441.3(FAAH):c.789G>A(p.Lys263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,614,220 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 36 hom. )

Consequence

FAAH
NM_001441.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.570

Variant links:

Genes affected

FAAH (HGNC:3553): (fatty acid amide hydrolase) This gene encodes a protein that is responsible for the hydrolysis of a number of primary and secondary fatty acid amides, including the neuromodulatory compounds anandamide and oleamide. [provided by RefSeq, Jul 2008]

FAAH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 1-46406041-G-A is Benign according to our data. Variant chr1-46406041-G-A is described in ClinVar as [Benign]. Clinvar id is 721205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.57 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0066 (1006/152350) while in subpopulation AFR AF= 0.0181 (753/41574). AF 95% confidence interval is 0.017. There are 12 homozygotes in gnomad4. There are 476 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3 linkuse as main transcript	c.789G>A	p.Lys263=	synonymous_variant	6/15	ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAAH	ENST00000243167.9 linkuse as main transcript	c.789G>A	p.Lys263=	synonymous_variant	6/15	1	NM_001441.3	P1
FAAH	ENST00000484697.5 linkuse as main transcript	c.72+247G>A		intron_variant, NMD_transcript_variant		1
FAAH	ENST00000489366.2 linkuse as main transcript	n.4G>A		non_coding_transcript_exon_variant	1/4	3
FAAH	ENST00000493735.5 linkuse as main transcript	n.1010G>A		non_coding_transcript_exon_variant	5/8	5

Frequencies

GnomAD3 genomes

AF:

0.00656

AC:

999

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0177

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00431

AC:

1084

AN:

251360

Hom.:

AF XY:

0.00436

AC XY:

592

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.0148

Gnomad SAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00219

AC:

3207

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00244

AC XY:

1777

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0199

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.0220

Gnomad4 SAS exome

AF:

0.0130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00660

AC:

1006

AN:

152350

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

476

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0178

Gnomad4 SAS

AF:

0.0172

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00220

Hom.:

Bravo

AF:

0.00660

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

7.3

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over