Variant chr20-25300697-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001042472.3(ABHD12):c.*148C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,542,216 control chromosomes in the GnomAD database, including 162,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16018 hom., cov: 33)

Exomes 𝑓: 0.45 ( 146204 hom. )

Consequence

ABHD12
NM_001042472.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.21

Variant links:

Genes affected

ABHD12 (HGNC:15868): (abhydrolase domain containing 12, lysophospholipase) This gene encodes an enzyme that catalyzes the hydrolysis of 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors, CB1 and CB2. The endocannabinoid system is involved in a wide range of physiological processes, including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation. Mutations in this gene are associated with the neurodegenerative disease, PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), resulting from an inborn error of endocannabinoid metabolism. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jan 2011]

ABHD12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 20-25300697-G-A is Benign according to our data. Variant chr20-25300697-G-A is described in ClinVar as [Benign]. Clinvar id is 337987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD12	NM_001042472.3 linkuse as main transcript	c.*148C>T		3_prime_UTR_variant	13/13	ENST00000339157.10	NP_001035937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD12	ENST00000339157.10 linkuse as main transcript	c.*148C>T		3_prime_UTR_variant	13/13	2	NM_001042472.3	ENSP00000341408	P1	Q8N2K0-1

Frequencies

GnomAD3 genomes

AF:

0.450

AC:

68379

AN:

151924

Hom.:

16009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.918

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.450

AC:

625796

AN:

1390174

Hom.:

146204

Cov.:

AF XY:

0.450

AC XY:

308931

AN XY:

686086

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.310

Gnomad4 EAS exome

AF:

0.916

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.450

AC:

68421

AN:

152042

Hom.:

16018

Cov.:

AF XY:

0.452

AC XY:

33563

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.918

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.428

Hom.:

4553

Bravo

AF:

0.445

Asia WGS

AF:

0.679

AC:

2359

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PHARC syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.071

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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