rs45476901

chr1-46408575-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_001441.3(FAAH):c.1068G>A(p.Ala356=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,614,136 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00091 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (9 hom.)
• Consequence: FAAH NM_001441.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP7: Synonymous conserved (PhyloP=-0.522 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3	c.1068G>A	p.Ala356=	synonymous_variant	8/15	ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAAH	ENST00000243167.9	c.1068G>A	p.Ala356=	synonymous_variant	8/15	1	NM_001441.3	P1
FAAH	ENST00000484697.5	c.*41G>A		3_prime_UTR_variant, NMD_transcript_variant	2/8	1
FAAH	ENST00000489366.2	n.283G>A		non_coding_transcript_exon_variant	3/4	3
FAAH	ENST00000493735.5	n.1289G>A		non_coding_transcript_exon_variant	7/8	5

Frequencies

GnomAD3 genomes AF: 0.000913 AC: 139 AN: 152178 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00127 AC: 319 AN: 251378 Hom.: 2 AF XY: 0.00147 AC XY: 200 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00268

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00180

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00162 AC: 2363 AN: 1461840 Hom.: 9 Cov.: 32 AF XY: 0.00167 AC XY: 1213 AN XY: 727220

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00300

Gnomad4 FIN exome AF: 0.000749

Gnomad4 NFE exome AF: 0.00172

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.000913 AC: 139 AN: 152296 Hom.: 1 Cov.: 32 AF XY: 0.000765 AC XY: 57 AN XY: 74462

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00130 Hom.: 1

Bravo AF: 0.00103

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	8.6
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs45476901; hg19: chr1-46874247; COSMIC: COSV54545174; COSMIC: COSV54545174;