chr20-25294917-GTTAGTT-G

Position:

• chr20-25294917-GTTAGTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015600.5(ABHD12):​c.*50_*55delAACTAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,598,252 control chromosomes in the GnomAD database, including 210,487 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19513 hom., cov: 0)
  • Exomes 𝑓: 0.51 (190974 hom.)
• Consequence: ABHD12 NM_015600.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.686

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 20-25294917-GTTAGTT-G is Benign according to our data. Variant chr20-25294917-GTTAGTT-G is described in ClinVar as [Benign]. Clinvar id is 1280514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYGB	NM_002862.4	c.2312+634_2312+639delAGTTTT		intron_variant		ENST00000216962.9	NP_002853.2
ABHD12	NM_015600.5	c.*50_*55delAACTAA		3_prime_UTR_variant	13/13		NP_056415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYGB	ENST00000216962.9	c.2312+634_2312+639delAGTTTT		intron_variant		1	NM_002862.4	ENSP00000216962.3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 75945 AN: 151184 Hom.: 19506 Cov.: 0

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.506 AC: 732421 AN: 1446950 Hom.: 190974 AF XY: 0.510 AC XY: 367363 AN XY: 720850

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.550

Gnomad4 ASJ exome AF: 0.451

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.640

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.517

GnomAD4 genome AF: 0.502 AC: 75985 AN: 151302 Hom.: 19513 Cov.: 0 AF XY: 0.508 AC XY: 37570 AN XY: 73888

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.487

Alfa AF: 0.489 Hom.: 2221

Bravo AF: 0.495

Asia WGS AF: 0.774 AC: 2690 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16436; hg19: chr20-25275553;