rs7020

Variant names:

• chr20-25297964-G-A
• rs7020
• NM_002862.4:c.*1442G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-25297964-G-A
• chr20-25297964-G-T

Variant summary

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

The NM_002862.4(PYGB):​c.*1442G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,136 control chromosomes in the GnomAD database, including 14,661 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 0.43 (14649 hom., cov: 34)
  • Exomes 𝑓: 0.51 (12 hom.)
• Consequence: PYGB NM_002862.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 23 publications found

Genes affected

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]

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=-0.81).
• 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
PYGB	NM_002862.4	c.*1442G>A		3_prime_UTR_variant	Exon 20 of 20	ENST00000216962.9	NP_002853.2
ABHD12	NM_015600.5	c.1158-2934C>T		intron_variant	Intron 12 of 12		NP_056415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.*1442G>A		3_prime_UTR_variant	Exon 20 of 20	1	NM_002862.4	ENSP00000216962.3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64875 AN: 151942 Hom.: 14644 Cov.: 34

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.514 AC: 38 AN: 74 Hom.: 12 Cov.: 0 AF XY: 0.442 AC XY: 23 AN XY: 52

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.593 AC: 32 AN: 54

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.427 AC: 64907 AN: 152062 Hom.: 14649 Cov.: 34 AF XY: 0.429 AC XY: 31869 AN XY: 74320

African (AFR) AF: 0.366 AC: 15187 AN: 41448

American (AMR) AF: 0.370 AC: 5660 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1078 AN: 3472

East Asian (EAS) AF: 0.918 AC: 4743 AN: 5168

South Asian (SAS) AF: 0.472 AC: 2274 AN: 4816

European-Finnish (FIN) AF: 0.449 AC: 4740 AN: 10566

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29798 AN: 67980

Other (OTH) AF: 0.403 AC: 851 AN: 2112

Alfa AF: 0.420 Hom.: 16188

Bravo AF: 0.420

Asia WGS AF: 0.674 AC: 2342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.25
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: rs7020; hg19: chr20-25278600;