chr7-107127911-C-T

Position:

• chr7-107127911-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002736.3(PRKAR2B):​c.397-301C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,176 control chromosomes in the GnomAD database, including 2,949 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 0.15 (2949 hom., cov: 32)
• Consequence: PRKAR2B NM_002736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333

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]

PRKAR2B-AS1 (HGNC:40472): (PRKAR2B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAR2B	NM_002736.3	c.397-301C>T		intron_variant		ENST00000265717.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAR2B	ENST00000265717.5	c.397-301C>T		intron_variant		1	NM_002736.3	P1
PRKAR2B-AS1	ENST00000627539.2	n.113+1123G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23366 AN: 152058 Hom.: 2948 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0901

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.154 AC: 23388 AN: 152176 Hom.: 2949 Cov.: 32 AF XY: 0.150 AC XY: 11160 AN XY: 74402

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0481

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0892 Hom.: 1175

Bravo AF: 0.167

Asia WGS AF: 0.110 AC: 382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs9656135; hg19: chr7-106768356;