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GeneBe

15-89191089-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_152924.5(ABHD2):c.936C>T(p.His312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,613,734 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 18 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 28 hom. )

Consequence

ABHD2
NM_152924.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.607
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-89191089-C-T is Benign according to our data. Variant chr15-89191089-C-T is described in ClinVar as [Benign]. Clinvar id is 787965.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.607 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0102 (1547/152242) while in subpopulation AFR AF= 0.0344 (1428/41522). AF 95% confidence interval is 0.0329. There are 18 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 18 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABHD2NM_152924.5 linkuse as main transcriptc.936C>T p.His312= synonymous_variant 9/11 ENST00000352732.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABHD2ENST00000352732.10 linkuse as main transcriptc.936C>T p.His312= synonymous_variant 9/111 NM_152924.5 P1
ABHD2ENST00000565973.5 linkuse as main transcriptc.936C>T p.His312= synonymous_variant 13/155 P1
ABHD2ENST00000568308.1 linkuse as main transcriptn.223C>T non_coding_transcript_exon_variant 3/43

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0101
AC:
1536
AN:
152124
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0342
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.0119
GnomAD3 exomes
AF:
0.00271
AC:
680
AN:
250834
Hom.:
12
AF XY:
0.00200
AC XY:
272
AN XY:
135678
show subpopulations
Gnomad AFR exome
AF:
0.0327
Gnomad AMR exome
AF:
0.00234
Gnomad ASJ exome
AF:
0.000596
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000360
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000379
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00135
AC:
1974
AN:
1461492
Hom.:
28
Cov.:
31
AF XY:
0.00124
AC XY:
898
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.0349
Gnomad4 AMR exome
AF:
0.00264
Gnomad4 ASJ exome
AF:
0.000842
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000383
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000345
Gnomad4 OTH exome
AF:
0.00325
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0102
AC:
1547
AN:
152242
Hom.:
18
Cov.:
32
AF XY:
0.00954
AC XY:
710
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0344
Gnomad4 AMR
AF:
0.00419
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00393
Hom.:
6
Bravo
AF:
0.0112
Asia WGS
AF:
0.00375
AC:
13
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.37
Cadd
Benign
5.9
Dann
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111401789; hg19: chr15-89734320; API