rs8028123

Positions:

• chr15-89163539-A-C

Variant summary

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

The NM_152924.5(ABHD2):​c.538+8005A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,168 control chromosomes in the GnomAD database, including 4,646 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 (4646 hom., cov: 33)
• Consequence: ABHD2 NM_152924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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]

ABHD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD2	NM_152924.5	c.538+8005A>C		intron_variant		ENST00000352732.10	NP_690888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD2	ENST00000352732.10	c.538+8005A>C		intron_variant		1	NM_152924.5	ENSP00000268129.5
ABHD2	ENST00000565973.5	c.538+8005A>C		intron_variant		5		ENSP00000455639.1
ABHD2	ENST00000562073.1	n.362+8005A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32192 AN: 152050 Hom.: 4612 Cov.: 33

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.212 AC: 32292 AN: 152168 Hom.: 4646 Cov.: 33 AF XY: 0.213 AC XY: 15830 AN XY: 74402

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.187

Alfa AF: 0.140 Hom.: 2394

Bravo AF: 0.214

Asia WGS AF: 0.162 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.76

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: rs8028123; hg19: chr15-89706770;