chr15-89073850-C-T

Position:

• chr15-89073850-C-T

Variant summary

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

The NM_001416423.1(ABHD2):​c.-195-1446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,960 control chromosomes in the GnomAD database, including 17,095 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 0.44 (17095 hom., cov: 31)
• Consequence: ABHD2 NM_001416423.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

ABHD2 (HGNC:18717): (abhydrolase domain containing 2, acylglycerol lipase) This gene encodes a protein containing an alpha/beta hydrolase fold, which is a catalytic domain found in a wide range of enzymes. The encoded protein is an acylglycerol lipase that catalyzes the hydrolysis of endocannabinoid arachidonoylglycerol from the cell membrane. This leads to activation of the sperm calcium channel CatSper, which results in sperm activation. Alternative splicing of this gene results in two transcript variants encoding the same protein. [provided by RefSeq, Jan 2017]

CARMAL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD2	NM_001416423.1	c.-195-1446C>T		intron_variant			NP_001403352.1
ABHD2	NM_001416424.1	c.-107+32550C>T		intron_variant			NP_001403353.1
CARMAL	NR_183880.1	n.405-1446C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARMAL	ENST00000565938.1	n.180-1446C>T		intron_variant		2
CARMAL	ENST00000668304.1	n.129-1446C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67114 AN: 151840 Hom.: 17094 Cov.: 31

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.442 AC: 67138 AN: 151960 Hom.: 17095 Cov.: 31 AF XY: 0.440 AC XY: 32665 AN XY: 74274

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.461

Alfa AF: 0.549 Hom.: 28137

Bravo AF: 0.415

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs420017; hg19: chr15-89617081;