chr1-46408711-A-G

Position:

• chr1-46408711-A-G

Variant summary

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

The NM_001441.3(FAAH):​c.1077+127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,433,316 control chromosomes in the GnomAD database, including 285,402 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 0.59 (27096 hom., cov: 32)
  • Exomes 𝑓: 0.63 (258306 hom.)
• Consequence: FAAH NM_001441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3	c.1077+127A>G		intron_variant		ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAAH	ENST00000243167.9	c.1077+127A>G		intron_variant		1	NM_001441.3	P1
FAAH	ENST00000484697.5	c.*50+127A>G		intron_variant, NMD_transcript_variant		1
FAAH	ENST00000489366.2	n.292+127A>G		intron_variant, non_coding_transcript_variant		3
FAAH	ENST00000493735.5	n.1298+127A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89792 AN: 151898 Hom.: 27106 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.633 AC: 810989 AN: 1281300 Hom.: 258306 AF XY: 0.631 AC XY: 407715 AN XY: 645856

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.584

Gnomad4 ASJ exome AF: 0.693

Gnomad4 EAS exome AF: 0.832

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.644

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.591 AC: 89804 AN: 152016 Hom.: 27096 Cov.: 32 AF XY: 0.593 AC XY: 44087 AN XY: 74308

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.585

Alfa AF: 0.493 Hom.: 1821

Bravo AF: 0.583

Asia WGS AF: 0.701 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.45

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: rs2295633; hg19: chr1-46874383; COSMIC: COSV54543508; COSMIC: COSV54543508;