rs7267979

Variant names:

• chr20-25317451-A-G
• rs7267979
• NM_001042472.3:c.543-373T>C

Variant summary

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

The NM_001042472.3(ABHD12):​c.543-373T>C 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 152,062 control chromosomes in the GnomAD database, including 25,544 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 (25544 hom., cov: 32)
• Consequence: ABHD12 NM_001042472.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 46 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042472.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD12	NM_001042472.3	MANE Select	c.543-373T>C		intron	N/A	NP_001035937.1
	ABHD12	NM_015600.5		c.543-373T>C		intron	N/A	NP_056415.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD12	ENST00000339157.10	TSL:2 MANE Select	c.543-373T>C		intron	N/A	ENSP00000341408.5
	ABHD12	ENST00000376542.8	TSL:1	c.543-373T>C		intron	N/A	ENSP00000365725.3
	ABHD12	ENST00000673121.1		c.175+1601T>C		intron	N/A	ENSP00000499839.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86703 AN: 151944 Hom.: 25512 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.0826

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.571 AC: 86790 AN: 152062 Hom.: 25544 Cov.: 32 AF XY: 0.569 AC XY: 42272 AN XY: 74324

African (AFR) AF: 0.633 AC: 26239 AN: 41474

American (AMR) AF: 0.625 AC: 9561 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2376 AN: 3472

East Asian (EAS) AF: 0.0822 AC: 425 AN: 5168

South Asian (SAS) AF: 0.528 AC: 2540 AN: 4812

European-Finnish (FIN) AF: 0.549 AC: 5810 AN: 10574

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

European-Non Finnish (NFE) AF: 0.559 AC: 37970 AN: 67954

Other (OTH) AF: 0.592 AC: 1249 AN: 2110

Alfa AF: 0.560 Hom.: 75735

Bravo AF: 0.578

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.23
PhyloP100		-0.43
PromoterAI		0.0024	Neutral
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: rs7267979; hg19: chr20-25298087;