NM_174912.4:c.996+11737C>T

Variant names:

• chrX-57392766-C-T
• rs2015312
• NM_174912.4:c.996+11737C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174912.4(FAAH2):​c.996+11737C>T variant causes a intron change. The variant allele was found at a frequency of 0.307 in 610,872 control chromosomes in the GnomAD database, including 22,167 homozygotes. There are 63,496 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 0.36 (6185 hom., 11452 hem., cov: 23)
  • Exomes 𝑓: 0.29 (15982 hom. 52044 hem.)
• Consequence: FAAH2 NM_174912.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.55
• Publications: 4 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]

MTHFD1P1 (HGNC:7433): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	NM_174912.4	MANE Select	c.996+11737C>T		intron	N/A	NP_777572.2	Q6GMR7
	FAAH2	NM_001353840.1		c.996+11737C>T		intron	N/A	NP_001340769.1
	FAAH2	NM_001353841.1		c.786+11737C>T		intron	N/A	NP_001340770.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH2	ENST00000374900.5	TSL:1 MANE Select	c.996+11737C>T		intron	N/A	ENSP00000364035.4	Q6GMR7
	FAAH2	ENST00000886040.1		c.1023+11737C>T		intron	N/A	ENSP00000556099.1
	FAAH2	ENST00000972153.1		c.897+11836C>T		intron	N/A	ENSP00000642212.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 40034 AN: 110608 Hom.: 6179 Cov.: 23

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.0997

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.613

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.294 AC: 147226 AN: 500213 Hom.: 15982 Cov.: 7 AF XY: 0.300 AC XY: 52044 AN XY: 173433

African (AFR) AF: 0.581 AC: 8566 AN: 14756

American (AMR) AF: 0.454 AC: 15458 AN: 34027

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 7208 AN: 15358

East Asian (EAS) AF: 0.323 AC: 8793 AN: 27241

South Asian (SAS) AF: 0.358 AC: 15259 AN: 42570

European-Finnish (FIN) AF: 0.173 AC: 6671 AN: 38638

Middle Eastern (MID) AF: 0.588 AC: 1785 AN: 3036

European-Non Finnish (NFE) AF: 0.250 AC: 74578 AN: 298656

Other (OTH) AF: 0.344 AC: 8908 AN: 25931

GnomAD4 genome AF: 0.362 AC: 40083 AN: 110659 Hom.: 6185 Cov.: 23 AF XY: 0.348 AC XY: 11452 AN XY: 32929

African (AFR) AF: 0.571 AC: 17273 AN: 30232

American (AMR) AF: 0.409 AC: 4282 AN: 10459

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1228 AN: 2622

East Asian (EAS) AF: 0.342 AC: 1190 AN: 3475

South Asian (SAS) AF: 0.367 AC: 959 AN: 2611

European-Finnish (FIN) AF: 0.163 AC: 974 AN: 5969

Middle Eastern (MID) AF: 0.606 AC: 129 AN: 213

European-Non Finnish (NFE) AF: 0.252 AC: 13325 AN: 52896

Other (OTH) AF: 0.437 AC: 655 AN: 1500

Alfa AF: 0.191 Hom.: 1242

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		5.5
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: rs2015312; hg19: chrX-57419199; COSMIC: COSV66512830;