NM_002736.3:c.481-4124G>T

Variant names:

• chr7-107136723-G-T
• rs9648946
• NM_002736.3:c.481-4124G>T

Variant summary

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

The NM_002736.3(PRKAR2B):​c.481-4124G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,068 control chromosomes in the GnomAD database, including 14,476 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 0.39 (14476 hom., cov: 32)
• Consequence: PRKAR2B NM_002736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 2 publications found

Genes affected

PRKAR2B (HGNC:9392): (protein kinase cAMP-dependent type II regulatory subunit beta) 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. This subunit has been shown to interact with and suppress the transcriptional activity of the cAMP responsive element binding protein 1 (CREB1) in activated T cells. Knockout studies in mice suggest that this subunit may play an important role in regulating energy balance and adiposity. The studies also suggest that this subunit may mediate the gene induction and cataleptic behavior induced by haloperidol. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002736.3. 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
	PRKAR2B	NM_002736.3	MANE Select	c.481-4124G>T		intron	N/A	NP_002727.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	ENST00000265717.5	TSL:1 MANE Select	c.481-4124G>T		intron	N/A	ENSP00000265717.4
	PRKAR2B	ENST00000706581.1		c.241-4124G>T		intron	N/A	ENSP00000516463.1
	PRKAR2B	ENST00000393613.6	TSL:3	n.536-4124G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59896 AN: 151950 Hom.: 14479 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.394 AC: 59894 AN: 152068 Hom.: 14476 Cov.: 32 AF XY: 0.399 AC XY: 29687 AN XY: 74332

African (AFR) AF: 0.101 AC: 4193 AN: 41500

American (AMR) AF: 0.490 AC: 7481 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2035 AN: 5156

South Asian (SAS) AF: 0.492 AC: 2366 AN: 4812

European-Finnish (FIN) AF: 0.579 AC: 6120 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34585 AN: 67956

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.435 Hom.: 2138

Bravo AF: 0.369

Asia WGS AF: 0.422 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.0
DANN	Benign	0.57
PhyloP100		0.53
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: rs9648946; hg19: chr7-106777168;