rs11584787

Positions:

• chr1-147156900-G-C
• chr1-147156900-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254101.4(PRKAB2):​c.*2665C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 152,090 control chromosomes in the GnomAD database, including 51,432 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 0.82 (51431 hom., cov: 30)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: PRKAB2 ENST00000254101.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

Genes affected

PRKAB2 (HGNC:9379): (protein kinase AMP-activated non-catalytic subunit beta 2) The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAB2	NM_005399.5	c.*2665C>G		3_prime_UTR_variant	8/8	ENST00000254101.4	NP_005390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAB2	ENST00000254101.4	c.*2665C>G		3_prime_UTR_variant	8/8	1	NM_005399.5	ENSP00000254101	P1

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123836 AN: 151968 Hom.: 51356 Cov.: 30

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.815 AC: 123969 AN: 152086 Hom.: 51431 Cov.: 30 AF XY: 0.824 AC XY: 61253 AN XY: 74354

Gnomad4 AFR AF: 0.952

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.793

Alfa AF: 0.758 Hom.: 6143

Bravo AF: 0.821

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11584787; hg19: chr1-146628479;