rs1046073

Variant names:

• chr20-25300697-G-A
• rs1046073
• NM_001042472.3:c.*148C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-25300697-G-A
• chr20-25300697-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.21
• Publications: 25 publications found

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 Gene-Disease associations (from GenCC):

• PHARC syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ABHD12	NM_001042472.3	c.*148C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000339157.10	NP_001035937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD12	ENST00000339157.10	c.*148C>T		3_prime_UTR_variant	Exon 13 of 13	2	NM_001042472.3	ENSP00000341408.5

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68379 AN: 151924 Hom.: 16009 Cov.: 33

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.: 41 AF XY: 0.450 AC XY: 308931 AN XY: 686086

African (AFR) AF: 0.432 AC: 13655 AN: 31584

American (AMR) AF: 0.326 AC: 11730 AN: 36030

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 7758 AN: 25032

East Asian (EAS) AF: 0.916 AC: 33002 AN: 36020

South Asian (SAS) AF: 0.461 AC: 36773 AN: 79708

European-Finnish (FIN) AF: 0.458 AC: 18253 AN: 39826

Middle Eastern (MID) AF: 0.361 AC: 1485 AN: 4110

European-Non Finnish (NFE) AF: 0.441 AC: 476682 AN: 1080034

Other (OTH) AF: 0.458 AC: 26458 AN: 57830

GnomAD4 genome AF: 0.450 AC: 68421 AN: 152042 Hom.: 16018 Cov.: 33 AF XY: 0.452 AC XY: 33563 AN XY: 74320

African (AFR) AF: 0.436 AC: 18102 AN: 41480

American (AMR) AF: 0.384 AC: 5873 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1096 AN: 3466

East Asian (EAS) AF: 0.918 AC: 4735 AN: 5158

South Asian (SAS) AF: 0.475 AC: 2283 AN: 4808

European-Finnish (FIN) AF: 0.451 AC: 4775 AN: 10582

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30073 AN: 67954

Other (OTH) AF: 0.424 AC: 894 AN: 2108

Alfa AF: 0.427 Hom.: 5042

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PHARC syndrome Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1046073; hg19: chr20-25281333;