rs5914101

Positions:

• chrX-57413512-G-A
• chrX-57413512-G-C

Variant summary

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

The NM_174912.4(FAAH2):​c.997-18406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 110,254 control chromosomes in the GnomAD database, including 5,080 homozygotes. There are 10,452 hemizygotes in GnomAD. 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 0.33 (5080 hom., 10452 hem., cov: 22)
• Consequence: FAAH2 NM_174912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

FAAH2 (HGNC:26440): (fatty acid amide hydrolase 2) This gene encodes a fatty acid amide hydrolase that shares a conserved protein motif with the amidase signature family of enzymes. The encoded enzyme is able to catalyze the hydrolysis of a broad range of bioactive lipids, including those from the three main classes of fatty acid amides; N-acylethanolamines, fatty acid primary amides and N-acyl amino acids. This enzyme has a preference for monounsaturated acyl chains as a substrate. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

FAAH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH2	NM_174912.4	c.997-18406G>A		intron_variant		ENST00000374900.5	NP_777572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAH2	ENST00000374900.5	c.997-18406G>A		intron_variant		1	NM_174912.4	ENSP00000364035.4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 36881 AN: 110199 Hom.: 5077 Cov.: 22 AF XY: 0.320 AC XY: 10418 AN XY: 32537

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.0963

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 36923 AN: 110254 Hom.: 5080 Cov.: 22 AF XY: 0.321 AC XY: 10452 AN XY: 32602

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.418

Alfa AF: 0.289 Hom.: 1832

Bravo AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.31

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: rs5914101; hg19: chrX-57439945;