1-46413890-T-G

Position:

• chr1-46413890-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 1-46413890-T-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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH	NM_001441.3			downstream_gene_variant		ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9			downstream_gene_variant		1	NM_001441.3	ENSP00000243167	P1
FAAH	ENST00000484697.5			downstream_gene_variant		1		ENSP00000481641

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

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.620

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.681

Gnomad4 NFE exome AF: 0.732

Gnomad4 OTH exome AF: 0.680

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

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.805

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.644

Alfa AF: 0.389 Hom.: 586

Bravo AF: 0.589

Asia WGS AF: 0.503 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.77
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295632; hg19: chr1-46879562;