20-25294981-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000376542.8(ABHD12):c.1207C>T(p.Leu403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,614,154 control chromosomes in the GnomAD database, including 329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.025 ( 146 hom., cov: 34)

Exomes 𝑓: 0.0039 ( 183 hom. )

Consequence

ABHD12
ENST00000376542.8 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.190

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:

PYGB (HGNC:9723): (glycogen phosphorylase B) The protein encoded by this gene is a glycogen phosphorylase found predominantly in the brain. The encoded protein forms homodimers which can associate into homotetramers, the enzymatically active form of glycogen phosphorylase. The activity of this enzyme is positively regulated by AMP and negatively regulated by ATP, ADP, and glucose-6-phosphate. This enzyme catalyzes the rate-determining step in glycogen degradation. [provided by RefSeq, Jul 2008]

PYGB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-25294981-G-A is Benign according to our data. Variant chr20-25294981-G-A is described in ClinVar as [Benign]. Clinvar id is 1228212.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-25294981-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PYGB	NM_002862.4 linkuse as main transcript	c.2313-623G>A		intron_variant		ENST00000216962.9
ABHD12	NM_015600.5 linkuse as main transcript	c.1207C>T	p.Leu403=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PYGB	ENST00000216962.9 linkuse as main transcript	c.2313-623G>A		intron_variant		1	NM_002862.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3782

AN:

152174

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0830

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00961

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00924

AC:

2324

AN:

251486

Hom.:

AF XY:

0.00800

AC XY:

1088

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0831

Gnomad AMR exome

AF:

0.00526

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00326

Gnomad SAS exome

AF:

0.0214

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00389

AC:

5688

AN:

1461862

Hom.:

183

Cov.:

AF XY:

0.00408

AC XY:

2967

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0841

Gnomad4 AMR exome

AF:

0.00575

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00209

Gnomad4 SAS exome

AF:

0.0197

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000308

Gnomad4 OTH exome

AF:

0.00735

GnomAD4 genome

AF:

0.0250

AC:

3801

AN:

152292

Hom.:

146

Cov.:

AF XY:

0.0237

AC XY:

1766

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0831

Gnomad4 AMR

AF:

0.00960

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00855

Hom.:

Bravo

AF:

0.0279

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000889

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

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

Cadd

Benign

0.78

Dann

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

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