Variant X-57286924-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_174912.4(FAAH2):c.99T>C(p.Gly33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,201,299 control chromosomes in the GnomAD database, including 45,773 homozygotes. There are 111,397 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.45 ( 11426 hom., 13405 hem., cov: 21)

Exomes 𝑓: 0.27 ( 34347 hom. 97992 hem. )

Consequence

FAAH2
NM_174912.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.539

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant X-57286924-T-C is Benign according to our data. Variant chrX-57286924-T-C is described in ClinVar as [Benign]. Clinvar id is 3056042.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-57286924-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.539 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH2	NM_174912.4 linkuse as main transcript	c.99T>C	p.Gly33=	synonymous_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.99T>C	p.Gly33=	synonymous_variant	1/11	1	NM_174912.4	P1

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

49239

AN:

108937

Hom.:

11414

Cov.:

AF XY:

0.426

AC XY:

13345

AN XY:

31303

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.0996

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.339

Gnomad SAS

AF:

0.368

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.502

GnomAD3 exomes

AF:

0.353

AC:

61289

AN:

173775

Hom.:

9996

AF XY:

0.324

AC XY:

19122

AN XY:

59067

show subpopulations

Gnomad AFR exome

AF:

0.904

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.360

GnomAD4 exome

AF:

0.274

AC:

299744

AN:

1092309

Hom.:

34347

Cov.:

AF XY:

0.273

AC XY:

97992

AN XY:

358655

show subpopulations

Gnomad4 AFR exome

AF:

0.911

Gnomad4 AMR exome

AF:

0.468

Gnomad4 ASJ exome

AF:

0.466

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.452

AC:

49314

AN:

108990

Hom.:

11426

Cov.:

AF XY:

0.427

AC XY:

13405

AN XY:

31366

show subpopulations

Gnomad4 AFR

AF:

0.888

Gnomad4 AMR

AF:

0.440

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.160

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.355

Hom.:

9132

Bravo

AF:

0.500

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FAAH2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 14, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.0

DANN

Benign

0.38

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