1-46413890-T-G

Variant names:

• chr1-46413890-T-G
• rs2295632
• NM_001441.3:c.*315T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001441.3(FAAH):​c.*315T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 438,500 control chromosomes in the GnomAD database, including 95,617 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 0.60 (29779 hom., cov: 32)
  • Exomes 𝑓: 0.67 (65838 hom.)
• Consequence: FAAH NM_001441.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	NM_001441.3	MANE Select	c.*315T>G		downstream_gene	N/A	NP_001432.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	ENST00000243167.9	TSL:1 MANE Select	c.*315T>G		downstream_gene	N/A	ENSP00000243167.8
	FAAH	ENST00000484697.5	TSL:1	n.*940T>G		downstream_gene	N/A	ENSP00000481641.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91648 AN: 151868 Hom.: 29791 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.669 AC: 191813 AN: 286514 Hom.: 65838 Cov.: 3 AF XY: 0.659 AC XY: 101501 AN XY: 154052

African (AFR) AF: 0.352 AC: 2845 AN: 8090

American (AMR) AF: 0.620 AC: 8411 AN: 13574

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 6262 AN: 7824

East Asian (EAS) AF: 0.512 AC: 7941 AN: 15500

South Asian (SAS) AF: 0.528 AC: 22892 AN: 43340

European-Finnish (FIN) AF: 0.681 AC: 10650 AN: 15630

Middle Eastern (MID) AF: 0.750 AC: 835 AN: 1114

European-Non Finnish (NFE) AF: 0.732 AC: 121613 AN: 166206

Other (OTH) AF: 0.680 AC: 10364 AN: 15236

GnomAD4 genome AF: 0.603 AC: 91671 AN: 151986 Hom.: 29779 Cov.: 32 AF XY: 0.600 AC XY: 44575 AN XY: 74300

African (AFR) AF: 0.358 AC: 14804 AN: 41406

American (AMR) AF: 0.616 AC: 9400 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2789 AN: 3464

East Asian (EAS) AF: 0.512 AC: 2638 AN: 5150

South Asian (SAS) AF: 0.530 AC: 2555 AN: 4822

European-Finnish (FIN) AF: 0.687 AC: 7277 AN: 10592

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49884 AN: 67972

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.518 Hom.: 1682

Bravo AF: 0.589

Asia WGS AF: 0.503 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.77
DANN	Benign	0.45
PhyloP100		-0.71
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2295632; hg19: chr1-46879562;