Variant chr1-46405089-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001441.3(FAAH):c.385C>A(p.Pro129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,776 control chromosomes in the GnomAD database, including 41,065 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5577 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35488 hom. )

Consequence

FAAH
NM_001441.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.386

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037901402).

BP6

Variant 1-46405089-C-A is Benign according to our data. Variant chr1-46405089-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 6724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH	NM_001441.3 linkuse as main transcript	c.385C>A	p.Pro129Thr	missense_variant	3/15	ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FAAH	ENST00000243167.9 linkuse as main transcript	c.385C>A	p.Pro129Thr	missense_variant	3/15	1	NM_001441.3	ENSP00000243167	P1
FAAH	ENST00000468718.5 linkuse as main transcript	n.405C>A		non_coding_transcript_exon_variant	3/5	3
FAAH	ENST00000493735.5 linkuse as main transcript	n.363C>A		non_coding_transcript_exon_variant	3/8	5

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39514

AN:

152014

Hom.:

5570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.176

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.236

AC:

59345

AN:

251362

Hom.:

7639

AF XY:

0.225

AC XY:

30632

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.226

GnomAD4 exome

AF:

0.215

AC:

314560

AN:

1461644

Hom.:

35488

Cov.:

AF XY:

0.214

AC XY:

155434

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.364

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.149

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.260

AC:

39553

AN:

152132

Hom.:

5577

Cov.:

AF XY:

0.261

AC XY:

19409

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.359

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.176

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.278

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.207

Hom.:

8871

Bravo

AF:

0.267

TwinsUK

AF:

0.206

AC:

765

ALSPAC

AF:

0.190

AC:

731

ESP6500AA

AF:

0.348

AC:

1533

ESP6500EA

AF:

0.200

AC:

1722

ExAC

AF:

0.233

AC:

28288

Asia WGS

AF:

0.192

AC:

669

AN:

3478

EpiCase

AF:

0.193

EpiControl

AF:

0.189

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

FAAH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

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). -

Polysubstance abuse, susceptibility to

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 08, 2021

- -

FAAH POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Apr 01, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.044

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.34

REVEL

Benign

0.061

Sift

Benign

0.32

Sift4G

Benign

0.46

Polyphen

0.014

Vest4

0.035

MPC

1.2

ClinPred

0.0028

GERP RS

3.1

Varity_R

0.12

gMVP

0.56

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