Variant chr1-46405702-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001441.3(FAAH):c.693C>G(p.Pro231=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00099 in 1,613,602 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 5 hom. )

Consequence

FAAH
NM_001441.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.09

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-46405702-C-G is Benign according to our data. Variant chr1-46405702-C-G is described in ClinVar as [Benign]. Clinvar id is 788507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00548 (835/152350) while in subpopulation AFR AF= 0.019 (791/41586). AF 95% confidence interval is 0.0179. There are 9 homozygotes in gnomad4. There are 401 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3 linkuse as main transcript	c.693C>G	p.Pro231=	synonymous_variant	5/15	ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAAH	ENST00000243167.9 linkuse as main transcript	c.693C>G	p.Pro231=	synonymous_variant	5/15	1	NM_001441.3	P1
FAAH	ENST00000468718.5 linkuse as main transcript	n.682C>G		non_coding_transcript_exon_variant	5/5	3
FAAH	ENST00000493735.5 linkuse as main transcript	n.671C>G		non_coding_transcript_exon_variant	5/8	5
FAAH	ENST00000484697.5 linkuse as main transcript			upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00140

AC:

350

AN:

250888

Hom.:

AF XY:

0.000994

AC XY:

135

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000521

AC:

762

AN:

1461252

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

324

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.00548

AC:

835

AN:

152350

Hom.:

Cov.:

AF XY:

0.00538

AC XY:

401

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000436

Hom.:

Bravo

AF:

0.00610

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.32

DANN

Benign

0.61

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