Variant 1-46405631-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001441.3(FAAH):c.622T>C(p.Trp208Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

FAAH
NM_001441.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.196

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056130707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3 linkuse as main transcript	c.622T>C	p.Trp208Arg	missense_variant	5/15	ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAAH	ENST00000243167.9 linkuse as main transcript	c.622T>C	p.Trp208Arg	missense_variant	5/15	1	NM_001441.3	P1
FAAH	ENST00000468718.5 linkuse as main transcript	n.611T>C		non_coding_transcript_exon_variant	5/5	3
FAAH	ENST00000493735.5 linkuse as main transcript	n.600T>C		non_coding_transcript_exon_variant	5/8	5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250512

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

The c.622T>C (p.W208R) alteration is located in exon 5 (coding exon 5) of the FAAH gene. This alteration results from a T to C substitution at nucleotide position 622, causing the tryptophan (W) at amino acid position 208 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.097

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.51

M_CAP

Benign

0.0084

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.39

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.68

REVEL

Benign

0.14

Sift

Benign

0.35

Sift4G

Benign

0.36

Polyphen

0.0010

Vest4

0.41

MutPred

0.76

Gain of disorder (P = 0.0126);

MVP

0.39

MPC

0.61

ClinPred

0.017

GERP RS

1.9

Varity_R

0.11

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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