Variant 3-58274820-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001320126.2(ABHD6):c.681+5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,612,462 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 26 hom. )

Consequence

ABHD6
NM_001320126.2 splice_region, intron

Scores

Splicing: ADA: 0.00001783

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.39

Variant links:

Genes affected

ABHD6 (HGNC:21398): (abhydrolase domain containing 6, acylglycerol lipase) Enables acylglycerol lipase activity. Involved in acylglycerol catabolic process. Predicted to be located in late endosome membrane and lysosomal membrane. Predicted to be integral component of membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and mitochondrion. Predicted to be integral component of postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ABHD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 3-58274820-C-T is Benign according to our data. Variant chr3-58274820-C-T is described in ClinVar as [Benign]. Clinvar id is 708984.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00849 (1294/152362) while in subpopulation AFR AF= 0.0298 (1238/41588). AF 95% confidence interval is 0.0284. There are 20 homozygotes in gnomad4. There are 610 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD6	NM_001320126.2 link	c.681+5C>T		splice_region_variant, intron_variant		ENST00000478253.6	NP_001307055.1	Q9BV23A0A024R323

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ABHD6	ENST00000478253.6 link	c.681+5C>T	splice_region_variant, intron_variant	2	NM_001320126.2	ENSP00000420315.1	Q9BV23
ABHD6	ENST00000295962.8 link	c.681+5C>T	splice_region_variant, intron_variant	1		ENSP00000295962.4	Q9BV23
ABHD6	ENST00000463756.5 link	c.*11C>T	downstream_gene_variant	3		ENSP00000420408.1	C9JNE7

Frequencies

GnomAD3 genomes

AF:

0.00848

AC:

1291

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00220

AC:

547

AN:

248904

Hom.:

AF XY:

0.00161

AC XY:

217

AN XY:

134588

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.00112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000800

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.000976

AC:

1425

AN:

1460100

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

599

AN XY:

726264

show subpopulations

Gnomad4 AFR exome

AF:

0.0350

Gnomad4 AMR exome

AF:

0.00133

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00849

AC:

1294

AN:

152362

Hom.:

Cov.:

AF XY:

0.00819

AC XY:

610

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0298

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00391

Hom.:

Bravo

AF:

0.00981

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.010

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over