Variant 1-46406301-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001441.3(FAAH):c.884G>A(p.Arg295Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,828 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

FAAH
NM_001441.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.14

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01320824).

BP6

Variant 1-46406301-G-A is Benign according to our data. Variant chr1-46406301-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 747912.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	7/15	ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAAH	ENST00000243167.9 linkuse as main transcript	c.884G>A	p.Arg295Gln	missense_variant	7/15	1	NM_001441.3	P1
FAAH	ENST00000484697.5 linkuse as main transcript	c.72+507G>A		intron_variant, NMD_transcript_variant		1
FAAH	ENST00000489366.2 linkuse as main transcript	n.99G>A		non_coding_transcript_exon_variant	2/4	3
FAAH	ENST00000493735.5 linkuse as main transcript	n.1105G>A		non_coding_transcript_exon_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.000887

AC:

135

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000956

GnomAD3 exomes

AF:

0.000282

AC:

AN:

251384

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00400

Gnomad AMR exome

AF:

0.000145

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:

0.000163

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461514

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.000112

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000886

AC:

135

AN:

152314

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00310

Gnomad4 AMR

AF:

0.000261

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:

0.000946

Alfa

AF:

0.000340

Hom.:

Bravo

AF:

0.00110

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000379

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.018

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.81

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

REVEL

Benign

0.076

Sift

Benign

0.21

Sift4G

Benign

0.17

Polyphen

0.0040

Vest4

0.10

MVP

0.75

MPC

0.39

ClinPred

0.014

GERP RS

3.3

Varity_R

0.12

gMVP

0.55

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