rs1981696

Variant names:

• chr7-107153655-C-T
• rs1981696
• NM_002736.3:c.918+404C>T

Variant summary

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

The ENST00000265717.5(PRKAR2B):​c.918+404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,140 control chromosomes in the GnomAD database, including 53,942 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 0.84 (53942 hom., cov: 31)
• Consequence: PRKAR2B ENST00000265717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 6 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265717.5. 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
	PRKAR2B	NM_002736.3	MANE Select	c.918+404C>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.918+404C>T		intron	N/A	ENSP00000265717.4
	PRKAR2B	ENST00000706580.1		n.1320C>T		non_coding_transcript_exon	Exon 8 of 8
	PRKAR2B	ENST00000706581.1		c.678+404C>T		intron	N/A	ENSP00000516463.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127778 AN: 152022 Hom.: 53891 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.841 AC: 127891 AN: 152140 Hom.: 53942 Cov.: 31 AF XY: 0.843 AC XY: 62672 AN XY: 74366

African (AFR) AF: 0.901 AC: 37383 AN: 41506

American (AMR) AF: 0.845 AC: 12927 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2664 AN: 3468

East Asian (EAS) AF: 0.929 AC: 4811 AN: 5180

South Asian (SAS) AF: 0.826 AC: 3978 AN: 4816

European-Finnish (FIN) AF: 0.840 AC: 8882 AN: 10578

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54544 AN: 67974

Other (OTH) AF: 0.832 AC: 1759 AN: 2114

Alfa AF: 0.829 Hom.: 9094

Bravo AF: 0.841

Asia WGS AF: 0.845 AC: 2939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.2
DANN	Benign	0.78
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: rs1981696; hg19: chr7-106794100;