rs4912407

Variant names:

• chr1-56647328-A-G
• rs4912407
• NM_006252.4:c.94+1847A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-56647328-A-G
• chr1-56647328-A-T

Variant summary

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

The NM_006252.4(PRKAA2):​c.94+1847A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,194 control chromosomes in the GnomAD database, including 57,737 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 0.87 (57737 hom., cov: 32)
• Consequence: PRKAA2 NM_006252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660
• Publications: 2 publications found

Genes affected

PRKAA2 (HGNC:9377): (protein kinase AMP-activated catalytic subunit alpha 2) The protein encoded by this gene is a catalytic 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. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008]

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 (AMR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	NM_006252.4	MANE Select	c.94+1847A>G		intron	N/A	NP_006243.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAA2	ENST00000371244.9	TSL:1 MANE Select	c.94+1847A>G		intron	N/A	ENSP00000360290.4	P54646
	PRKAA2	ENST00000860136.1		c.94+1847A>G		intron	N/A	ENSP00000530195.1
	PRKAA2	ENST00000860138.1		c.94+1847A>G		intron	N/A	ENSP00000530197.1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132348 AN: 152076 Hom.: 57685 Cov.: 32

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.884

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

GnomAD4 genome AF: 0.870 AC: 132458 AN: 152194 Hom.: 57737 Cov.: 32 AF XY: 0.870 AC XY: 64740 AN XY: 74402

African (AFR) AF: 0.856 AC: 35533 AN: 41526

American (AMR) AF: 0.886 AC: 13548 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3148 AN: 3472

East Asian (EAS) AF: 0.793 AC: 4100 AN: 5168

South Asian (SAS) AF: 0.744 AC: 3580 AN: 4814

European-Finnish (FIN) AF: 0.913 AC: 9672 AN: 10598

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59948 AN: 68010

Other (OTH) AF: 0.880 AC: 1861 AN: 2114

Alfa AF: 0.853 Hom.: 2976

Bravo AF: 0.871

Asia WGS AF: 0.820 AC: 2846 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.7
DANN	Benign	0.83
PhyloP100		0.066
Mutation Taster		=100/0	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: rs4912407; hg19: chr1-57113001;