chr20-25336720-T-C

Variant names:

• chr20-25336720-T-C
• rs6083805
• NM_001042472.3:c.316+2507A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042472.3(ABHD12):​c.316+2507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,056 control chromosomes in the GnomAD database, including 25,525 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (25525 hom., cov: 32)
• Consequence: ABHD12 NM_001042472.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD12	NM_001042472.3	c.316+2507A>G		intron_variant	Intron 2 of 12	ENST00000339157.10	NP_001035937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD12	ENST00000339157.10	c.316+2507A>G		intron_variant	Intron 2 of 12	2	NM_001042472.3	ENSP00000341408.5

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86695 AN: 151938 Hom.: 25493 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.0828

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.596

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86781 AN: 152056 Hom.: 25525 Cov.: 32 AF XY: 0.569 AC XY: 42257 AN XY: 74330

African (AFR) AF: 0.632 AC: 26224 AN: 41480

American (AMR) AF: 0.626 AC: 9561 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2372 AN: 3468

East Asian (EAS) AF: 0.0824 AC: 426 AN: 5168

South Asian (SAS) AF: 0.528 AC: 2544 AN: 4822

European-Finnish (FIN) AF: 0.548 AC: 5795 AN: 10566

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37989 AN: 67954

Other (OTH) AF: 0.593 AC: 1252 AN: 2112

Alfa AF: 0.566 Hom.: 3602

Bravo AF: 0.578

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.83
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6083805; hg19: chr20-25317356;