rs420017

Variant names:

• chr15-89073850-C-T
• rs420017
• NM_001416423.1:c.-195-1446C>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.-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
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001416423.1. 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
	ABHD2	NM_001416423.1		c.-195-1446C>T		intron	N/A	NP_001403352.1	A0A024RC89
	ABHD2	NM_001416424.1		c.-107+32550C>T		intron	N/A	NP_001403353.1	P08910
	CARMAL	NR_183880.1		n.405-1446C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMAL	ENST00000565938.2	TSL:2	n.393-1446C>T		intron	N/A
	CARMAL	ENST00000668304.1		n.129-1446C>T		intron	N/A
	CARMAL	ENST00000757230.1		n.307-1446C>T		intron	N/A

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

African (AFR) AF: 0.203 AC: 8412 AN: 41436

American (AMR) AF: 0.400 AC: 6100 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1434 AN: 5172

South Asian (SAS) AF: 0.557 AC: 2678 AN: 4812

European-Finnish (FIN) AF: 0.544 AC: 5739 AN: 10540

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39618 AN: 67952

Other (OTH) AF: 0.461 AC: 971 AN: 2106

Alfa AF: 0.519 Hom.: 44185

Bravo AF: 0.415

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.62
DANN	Benign	0.56
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs420017; hg19: chr15-89617081;