rs17159890

chr1-147156795-A-C

Variant summary

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

The NM_005399.5(PRKAB2):c.*2770T>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 0.0511 in 152,238 control chromosomes in the GnomAD database, including 343 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 0.051 (343 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKAB2 NM_005399.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAB2	NM_005399.5	c.*2770T>G		3_prime_UTR_variant	8/8	ENST00000254101.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAB2	ENST00000254101.4	c.*2770T>G		3_prime_UTR_variant	8/8	1	NM_005399.5	P1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7764 AN: 152120 Hom.: 342 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.0365

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0943

Gnomad FIN AF: 0.00263

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0478

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0511 AC: 7774 AN: 152238 Hom.: 343 Cov.: 32 AF XY: 0.0498 AC XY: 3709 AN XY: 74442

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0365

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.00263

Gnomad4 NFE AF: 0.0273

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0339 Hom.: 162

Bravo AF: 0.0548

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.0
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs17159890; hg19: chr1-146628374;