rs3766522

Positions:

• chr1-147170107-A-T

Variant summary

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

The NM_005399.5(PRKAB2):​c.156+1882T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,164 control chromosomes in the GnomAD database, including 3,423 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 0.20 (3423 hom., cov: 32)
• Consequence: PRKAB2 NM_005399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAB2	NM_005399.5	c.156+1882T>A		intron_variant		ENST00000254101.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAB2	ENST00000254101.4	c.156+1882T>A		intron_variant		1	NM_005399.5	P1
PRKAB2	ENST00000474939.1	n.301+1882T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31150 AN: 152046 Hom.: 3420 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31172 AN: 152164 Hom.: 3423 Cov.: 32 AF XY: 0.206 AC XY: 15304 AN XY: 74394

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.207

Alfa AF: 0.233 Hom.: 550

Bravo AF: 0.198

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.2
DANN	Benign	0.67

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: rs3766522; hg19: chr1-146641686;