chr20-25294917-GTTAGTT-G

Variant names:

• chr20-25294917-GTTAGTT-G
• rs16436
• ENST00000376542.8:c.*50_*55delAACTAA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015600.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PYGB	NM_002862.4	MANE Select	c.2312+634_2312+639delAGTTTT		intron	N/A	NP_002853.2
	ABHD12	NM_015600.5		c.*50_*55delAACTAA		3_prime_UTR	Exon 13 of 13	NP_056415.1	Q8N2K0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD12	ENST00000376542.8	TSL:1	c.*50_*55delAACTAA		3_prime_UTR	Exon 13 of 13	ENSP00000365725.3	Q8N2K0-2
	PYGB	ENST00000216962.9	TSL:1 MANE Select	c.2312+634_2312+639delAGTTTT		intron	N/A	ENSP00000216962.3	P11216
	ABHD12	ENST00000672871.1		c.*50_*55delAACTAA		3_prime_UTR	Exon 7 of 7	ENSP00000499949.1	A0A5F9ZGZ9

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

African (AFR) AF: 0.450 AC: 14873 AN: 33076

American (AMR) AF: 0.550 AC: 24592 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 11742 AN: 26028

East Asian (EAS) AF: 0.920 AC: 36487 AN: 39642

South Asian (SAS) AF: 0.640 AC: 54991 AN: 85972

European-Finnish (FIN) AF: 0.511 AC: 27219 AN: 53318

Middle Eastern (MID) AF: 0.442 AC: 2414 AN: 5462

European-Non Finnish (NFE) AF: 0.482 AC: 529189 AN: 1098920

Other (OTH) AF: 0.517 AC: 30914 AN: 59846

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

African (AFR) AF: 0.453 AC: 18678 AN: 41276

American (AMR) AF: 0.536 AC: 8147 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1599 AN: 3456

East Asian (EAS) AF: 0.926 AC: 4717 AN: 5094

South Asian (SAS) AF: 0.658 AC: 3149 AN: 4788

European-Finnish (FIN) AF: 0.511 AC: 5354 AN: 10480

Middle Eastern (MID) AF: 0.465 AC: 134 AN: 288

European-Non Finnish (NFE) AF: 0.483 AC: 32683 AN: 67712

Other (OTH) AF: 0.487 AC: 1024 AN: 2102

Alfa AF: 0.489 Hom.: 2221

Bravo AF: 0.495

Asia WGS AF: 0.774 AC: 2690 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16436; hg19: chr20-25275553; COSMIC: COSV53816463;