rs16942644

Variant names:

• chr15-89069505-G-A
• rs16942644
• NM_001416423.1:c.-296-586G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-89069505-G-A
• chr15-89069505-G-T

Variant summary

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

The NM_001416423.1(ABHD2):​c.-296-586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,580 control chromosomes in the GnomAD database, including 4,194 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 0.21 (4194 hom., cov: 29)
• Consequence: ABHD2 NM_001416423.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• Publications: 6 publications found

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:55102): (coronary artery disease region linked MFGE8 regulatory lncRNA)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD2	NM_001416423.1	c.-296-586G>A		intron_variant	Intron 1 of 12		NP_001403352.1
ABHD2	NM_001416424.1	c.-107+28205G>A		intron_variant	Intron 1 of 10		NP_001403353.1
CARMAL	NR_183880.1	n.304-586G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARMAL	ENST00000565938.2	n.292-586G>A		intron_variant	Intron 1 of 3	2
CARMAL	ENST00000668304.1	n.28-586G>A		intron_variant	Intron 1 of 3
CARMAL	ENST00000757230.1	n.307-5791G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31612 AN: 151462 Hom.: 4185 Cov.: 29

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.209 AC: 31662 AN: 151580 Hom.: 4194 Cov.: 29 AF XY: 0.213 AC XY: 15773 AN XY: 74026

African (AFR) AF: 0.356 AC: 14705 AN: 41266

American (AMR) AF: 0.216 AC: 3286 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 650 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1809 AN: 5144

South Asian (SAS) AF: 0.263 AC: 1265 AN: 4808

European-Finnish (FIN) AF: 0.141 AC: 1466 AN: 10430

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.118 AC: 8011 AN: 67916

Other (OTH) AF: 0.193 AC: 408 AN: 2110

Alfa AF: 0.182 Hom.: 572

Bravo AF: 0.220

Asia WGS AF: 0.281 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs16942644; hg19: chr15-89612736;