rs41309147

Positions:

• chr1-46406203-G-A
• chr1-46406203-G-C

Variant summary

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

The NM_001441.3(FAAH):​c.827-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 1,613,836 control chromosomes in the GnomAD database, including 7,920 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 0.070 (492 hom., cov: 33)
  • Exomes 𝑓: 0.096 (7428 hom.)
• Consequence: FAAH NM_001441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH	NM_001441.3	c.827-41G>A		intron_variant		ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9	c.827-41G>A		intron_variant		1	NM_001441.3	ENSP00000243167.8
FAAH	ENST00000484697.5	n.71+409G>A		intron_variant		1		ENSP00000481641.1
FAAH	ENST00000489366.2	n.42-41G>A		intron_variant		3
FAAH	ENST00000493735.5	n.1048-41G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0704 AC: 10702 AN: 152114 Hom.: 493 Cov.: 33

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.106

GnomAD3 exomes AF: 0.0848 AC: 21292 AN: 251216 Hom.: 1209 AF XY: 0.0934 AC XY: 12681 AN XY: 135820

Gnomad AFR exome AF: 0.0195

Gnomad AMR exome AF: 0.0511

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.000707

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.0514

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0985

GnomAD4 exome AF: 0.0962 AC: 140633 AN: 1461604 Hom.: 7428 Cov.: 58 AF XY: 0.0988 AC XY: 71861 AN XY: 727124

Gnomad4 AFR exome AF: 0.0194

Gnomad4 AMR exome AF: 0.0538

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.000705

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0943

GnomAD4 genome AF: 0.0703 AC: 10705 AN: 152232 Hom.: 492 Cov.: 33 AF XY: 0.0698 AC XY: 5197 AN XY: 74446

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0619

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0901 Hom.: 127

Bravo AF: 0.0669

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.74

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: rs41309147; hg19: chr1-46871875; COSMIC: COSV54546193; COSMIC: COSV54546193;