3-48799749-T-C

Variant names:

• chr3-48799749-T-C
• rs9859473
• NM_004157.4:c.299-5700A>G

Variant summary

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

The NM_004157.4(PRKAR2A):​c.299-5700A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,236 control chromosomes in the GnomAD database, including 51,301 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 (51301 hom., cov: 33)
• Consequence: PRKAR2A NM_004157.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 12 publications found

Genes affected

PRKAR2A (HGNC:9391): (protein kinase cAMP-dependent type II regulatory subunit alpha) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. It may interact with various A-kinase anchoring proteins and determine the subcellular localization of cAMP-dependent protein kinase. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER). [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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAR2A	NM_004157.4	c.299-5700A>G		intron_variant	Intron 2 of 10	ENST00000265563.13	NP_004148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAR2A	ENST00000265563.13	c.299-5700A>G		intron_variant	Intron 2 of 10	1	NM_004157.4	ENSP00000265563.8

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124411 AN: 152118 Hom.: 51253 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.818 AC: 124519 AN: 152236 Hom.: 51301 Cov.: 33 AF XY: 0.824 AC XY: 61352 AN XY: 74434

African (AFR) AF: 0.881 AC: 36610 AN: 41542

American (AMR) AF: 0.845 AC: 12907 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2976 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5184

South Asian (SAS) AF: 0.942 AC: 4544 AN: 4824

European-Finnish (FIN) AF: 0.808 AC: 8573 AN: 10608

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51127 AN: 68016

Other (OTH) AF: 0.807 AC: 1702 AN: 2110

Alfa AF: 0.788 Hom.: 29168

Bravo AF: 0.824

Asia WGS AF: 0.965 AC: 3357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.29
PhyloP100		-1.4
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: rs9859473; hg19: chr3-48837182;