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. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAH2	NM_174912.4	c.996+11737C>T		intron_variant	Intron 7 of 10	ENST00000374900.5	NP_777572.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAH2	ENST00000374900.5	c.996+11737C>T		intron_variant	Intron 7 of 10	1	NM_174912.4	ENSP00000364035.4
MTHFD1P1	ENST00000413059.1	n.2644G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.362 AC: 40034 AN: 110608 Hom.: 6179 Cov.: 23 AF XY: 0.347 AC XY: 11412 AN XY: 32868

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

Gnomad4 AFR exome AF: 0.581

Gnomad4 AMR exome AF: 0.454

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.344

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

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.437

Alfa AF: 0.191 Hom.: 1242

Bravo AF: 0.397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.69

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: rs2015312; hg19: chrX-57419199; COSMIC: COSV66512830;