1-147156900-G-C

Variant names:

• chr1-147156900-G-C
• rs11584787
• NM_005399.5:c.*2665C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005399.5(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 NM_005399.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PRKAB2	NM_005399.5	c.*2665C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000254101.4	NP_005390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAB2	ENST00000254101.4	c.*2665C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_005399.5	ENSP00000254101.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.952 AC: 39521 AN: 41532

American (AMR) AF: 0.849 AC: 12960 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2429 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4847 AN: 5156

South Asian (SAS) AF: 0.923 AC: 4447 AN: 4818

European-Finnish (FIN) AF: 0.814 AC: 8624 AN: 10596

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48517 AN: 67924

Other (OTH) AF: 0.793 AC: 1674 AN: 2112

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
PhyloP100		0.31

Splicing

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

Other links and lift over

dbSNP: rs11584787; hg19: chr1-146628479;