Variant X-57286949-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_174912.4(FAAH2):c.124C>T(p.Arg42Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0086 in 1,200,848 control chromosomes in the GnomAD database, including 36 homozygotes. There are 3,267 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 4 hom., 176 hem., cov: 21)

Exomes 𝑓: 0.0088 ( 32 hom. 3091 hem. )

Consequence

FAAH2
NM_174912.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.808

Variant links:

Genes affected

FAAH2 (HGNC:26440): (fatty acid amide hydrolase 2) This gene encodes a fatty acid amide hydrolase that shares a conserved protein motif with the amidase signature family of enzymes. The encoded enzyme is able to catalyze the hydrolysis of a broad range of bioactive lipids, including those from the three main classes of fatty acid amides; N-acylethanolamines, fatty acid primary amides and N-acyl amino acids. This enzyme has a preference for monounsaturated acyl chains as a substrate. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

FAAH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004681617).

BP6

Variant X-57286949-C-T is Benign according to our data. Variant chrX-57286949-C-T is described in ClinVar as [Benign]. Clinvar id is 771788.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH2	NM_174912.4 linkuse as main transcript	c.124C>T	p.Arg42Trp	missense_variant	1/11	ENST00000374900.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAAH2	ENST00000374900.5 linkuse as main transcript	c.124C>T	p.Arg42Trp	missense_variant	1/11	1	NM_174912.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00640

AC:

708

AN:

110618

Hom.:

Cov.:

AF XY:

0.00536

AC XY:

176

AN XY:

32818

show subpopulations

Gnomad AFR

AF:

0.00132

Gnomad AMI

AF:

0.00292

Gnomad AMR

AF:

0.00442

Gnomad ASJ

AF:

0.0174

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00195

Gnomad FIN

AF:

0.00410

Gnomad MID

AF:

0.0254

Gnomad NFE

AF:

0.00998

Gnomad OTH

AF:

0.00747

GnomAD3 exomes

AF:

0.00715

AC:

1228

AN:

171787

Hom.:

AF XY:

0.00674

AC XY:

386

AN XY:

57279

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.00315

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00198

Gnomad FIN exome

AF:

0.00578

Gnomad NFE exome

AF:

0.0112

Gnomad OTH exome

AF:

0.00858

GnomAD4 exome

AF:

0.00883

AC:

9625

AN:

1090177

Hom.:

Cov.:

AF XY:

0.00867

AC XY:

3091

AN XY:

356459

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.00612

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00851

GnomAD4 genome

AF:

0.00636

AC:

704

AN:

110671

Hom.:

Cov.:

AF XY:

0.00535

AC XY:

176

AN XY:

32881

show subpopulations

Gnomad4 AFR

AF:

0.00131

Gnomad4 AMR

AF:

0.00442

Gnomad4 ASJ

AF:

0.0174

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00195

Gnomad4 FIN

AF:

0.00410

Gnomad4 NFE

AF:

0.00998

Gnomad4 OTH

AF:

0.00737

Alfa

AF:

0.0105

Hom.:

478

Bravo

AF:

0.00638

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0111

AC:

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.0113

AC:

ExAC

AF:

0.00772

AC:

937

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 25, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.10

Sift

Uncertain

0.021

Sift4G

Uncertain

0.020

Polyphen

0.93

Vest4

0.086

MVP

0.38

MPC

0.0011

ClinPred

0.035

GERP RS

-0.58

Varity_R

0.080

gMVP

0.43

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