chrX-57413512-G-A

Variant names:

• chrX-57413512-G-A
• rs5914101
• NM_174912.4:c.997-18406G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174912.4. 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
	FAAH2	NM_174912.4	MANE Select	c.997-18406G>A		intron	N/A	NP_777572.2
	FAAH2	NM_001353840.1		c.996+32483G>A		intron	N/A	NP_001340769.1
	FAAH2	NM_001353841.1		c.787-18406G>A		intron	N/A	NP_001340770.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	ENST00000374900.5	TSL:1 MANE Select	c.997-18406G>A		intron	N/A	ENSP00000364035.4
	FAAH2	ENST00000886040.1		c.1024-18406G>A		intron	N/A	ENSP00000556099.1
	FAAH2	ENST00000972153.1		c.898-18406G>A		intron	N/A	ENSP00000642212.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 36881 AN: 110199 Hom.: 5077 Cov.: 22

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

African (AFR) AF: 0.475 AC: 14380 AN: 30248

American (AMR) AF: 0.398 AC: 4121 AN: 10366

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1229 AN: 2613

East Asian (EAS) AF: 0.341 AC: 1191 AN: 3493

South Asian (SAS) AF: 0.372 AC: 964 AN: 2593

European-Finnish (FIN) AF: 0.161 AC: 943 AN: 5844

Middle Eastern (MID) AF: 0.613 AC: 130 AN: 212

European-Non Finnish (NFE) AF: 0.252 AC: 13270 AN: 52703

Other (OTH) AF: 0.418 AC: 630 AN: 1507

Alfa AF: 0.289 Hom.: 1832

Bravo AF: 0.366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.31
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5914101; hg19: chrX-57439945;