chr12-119667935-C-A

Variant names:

• chr12-119667935-C-A
• rs6490266
• ENST00000541640.5:c.-120C>A

Variant summary

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

The ENST00000541640.5(PRKAB1):​c.-120C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 362,580 control chromosomes in the GnomAD database, including 15,968 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 0.30 (7488 hom., cov: 34)
  • Exomes 𝑓: 0.27 (8480 hom.)
• Consequence: PRKAB1 ENST00000541640.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 6 publications found

Genes affected

PRKAB1 (HGNC:9378): (protein kinase AMP-activated non-catalytic subunit beta 1) 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. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex. [provided by RefSeq, Jul 2008]

ENSG00000248636 (HGNC:58183):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000541640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAB1-AS1	NR_188490.1		n.185+8G>T		splice_region intron	N/A
	PRKAB1-AS1	NR_188492.1		n.185+8G>T		splice_region intron	N/A
	PRKAB1-AS1	NR_188494.1		n.185+8G>T		splice_region intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAB1	ENST00000541640.5	TSL:1	c.-120C>A		5_prime_UTR	Exon 1 of 8	ENSP00000441369.1
	ENSG00000248636	ENST00000537366.6	TSL:3	n.153+8G>T		splice_region intron	N/A
	ENSG00000248636	ENST00000815425.1		n.566+8G>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46132 AN: 152206 Hom.: 7481 Cov.: 34

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.269 AC: 56657 AN: 210256 Hom.: 8480 Cov.: 2 AF XY: 0.267 AC XY: 28969 AN XY: 108620

African (AFR) AF: 0.384 AC: 1864 AN: 4854

American (AMR) AF: 0.210 AC: 846 AN: 4026

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 1919 AN: 7518

East Asian (EAS) AF: 0.0185 AC: 215 AN: 11598

South Asian (SAS) AF: 0.201 AC: 4140 AN: 20646

European-Finnish (FIN) AF: 0.229 AC: 3420 AN: 14964

Middle Eastern (MID) AF: 0.321 AC: 347 AN: 1082

European-Non Finnish (NFE) AF: 0.303 AC: 40041 AN: 131986

Other (OTH) AF: 0.285 AC: 3865 AN: 13582

GnomAD4 genome AF: 0.303 AC: 46160 AN: 152324 Hom.: 7488 Cov.: 34 AF XY: 0.294 AC XY: 21937 AN XY: 74498

African (AFR) AF: 0.385 AC: 16009 AN: 41560

American (AMR) AF: 0.245 AC: 3747 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 952 AN: 3472

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5196

South Asian (SAS) AF: 0.190 AC: 920 AN: 4832

European-Finnish (FIN) AF: 0.237 AC: 2516 AN: 10620

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21082 AN: 68022

Other (OTH) AF: 0.292 AC: 617 AN: 2112

Alfa AF: 0.195 Hom.: 398

Bravo AF: 0.306

Asia WGS AF: 0.131 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.41
DANN	Benign	0.70
PhyloP100		-2.3
PromoterAI		-0.14	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6490266; hg19: chr12-120105740;