15-89195345-C-T

Variant names:

• chr15-89195345-C-T
• rs147741950
• NM_152924.5:c.1200C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_152924.5(ABHD2):​c.1200C>T​(p.Tyr400Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 1,614,196 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (64 hom.)
• Consequence: ABHD2 NM_152924.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 15-89195345-C-T is Benign according to our data. Variant chr15-89195345-C-T is described in ClinVar as Benign. ClinVar VariationId is 777877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152924.5. 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_152924.5	MANE Select	c.1200C>T	p.Tyr400Tyr	synonymous	Exon 11 of 11	NP_690888.1	A0A024RC89
	ABHD2	NM_001416412.1		c.1200C>T	p.Tyr400Tyr	synonymous	Exon 13 of 13	NP_001403341.1	A0A024RC89
	ABHD2	NM_001416413.1		c.1200C>T	p.Tyr400Tyr	synonymous	Exon 14 of 14	NP_001403342.1	A0A024RC89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD2	ENST00000352732.10	TSL:1 MANE Select	c.1200C>T	p.Tyr400Tyr	synonymous	Exon 11 of 11	ENSP00000268129.5	P08910
	ABHD2	ENST00000565973.5	TSL:5	c.1200C>T	p.Tyr400Tyr	synonymous	Exon 15 of 15	ENSP00000455639.1	P08910
	ABHD2	ENST00000864961.1		c.1200C>T	p.Tyr400Tyr	synonymous	Exon 10 of 10	ENSP00000535020.1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00616 AC: 1549 AN: 251342 AF XY: 0.00687

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.00893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.00641

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00682 AC: 9967 AN: 1461884 Hom.: 64 Cov.: 31 AF XY: 0.00703 AC XY: 5113 AN XY: 727244

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.00470 AC: 210 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00830 AC: 217 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0144 AC: 1240 AN: 86258

European-Finnish (FIN) AF: 0.00502 AC: 268 AN: 53416

Middle Eastern (MID) AF: 0.0102 AC: 59 AN: 5768

European-Non Finnish (NFE) AF: 0.00675 AC: 7508 AN: 1112010

Other (OTH) AF: 0.00705 AC: 426 AN: 60396

GnomAD4 genome AF: 0.00491 AC: 748 AN: 152312 Hom.: 3 Cov.: 32 AF XY: 0.00477 AC XY: 355 AN XY: 74490

African (AFR) AF: 0.00144 AC: 60 AN: 41564

American (AMR) AF: 0.00366 AC: 56 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4834

European-Finnish (FIN) AF: 0.00650 AC: 69 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00666 AC: 453 AN: 68024

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00635 Hom.: 8

Bravo AF: 0.00462

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00791

EpiControl AF: 0.00640

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.8
DANN	Benign	0.56
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs147741950; hg19: chr15-89738576;