7-107159513-C-T

Variant names:

• chr7-107159513-C-T
• rs76484258
• NM_002736.3:c.1188C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002736.3(PRKAR2B):​c.1188C>T​(p.Ile396Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00501 in 1,613,984 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (38 hom.)
• Consequence: PRKAR2B NM_002736.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0210
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 7-107159513-C-T is Benign according to our data. Variant chr7-107159513-C-T is described in ClinVar as Benign. ClinVar VariationId is 786743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.021 with no splicing effect.
• BS2: High AC in GnomAd4 at 680 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	NM_002736.3	MANE Select	c.1188C>T	p.Ile396Ile	synonymous	Exon 11 of 11	NP_002727.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	ENST00000265717.5	TSL:1 MANE Select	c.1188C>T	p.Ile396Ile	synonymous	Exon 11 of 11	ENSP00000265717.4	P31323
	PRKAR2B	ENST00000854598.1		c.1272C>T	p.Ile424Ile	synonymous	Exon 12 of 12	ENSP00000524657.1
	PRKAR2B	ENST00000913925.1		c.1182C>T	p.Ile394Ile	synonymous	Exon 11 of 11	ENSP00000583984.1

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 680 AN: 152144 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00542

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00504 AC: 1267 AN: 251446 AF XY: 0.00595

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00506

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00507 AC: 7409 AN: 1461722 Hom.: 38 Cov.: 30 AF XY: 0.00551 AC XY: 4009 AN XY: 727168

African (AFR) AF: 0.000896 AC: 30 AN: 33478

American (AMR) AF: 0.00369 AC: 165 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00723 AC: 189 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39688

South Asian (SAS) AF: 0.0154 AC: 1327 AN: 86244

European-Finnish (FIN) AF: 0.000899 AC: 48 AN: 53420

Middle Eastern (MID) AF: 0.0165 AC: 95 AN: 5768

European-Non Finnish (NFE) AF: 0.00472 AC: 5245 AN: 1111884

Other (OTH) AF: 0.00508 AC: 307 AN: 60386

GnomAD4 genome AF: 0.00447 AC: 680 AN: 152262 Hom.: 4 Cov.: 32 AF XY: 0.00433 AC XY: 322 AN XY: 74446

African (AFR) AF: 0.000987 AC: 41 AN: 41546

American (AMR) AF: 0.00923 AC: 141 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0154 AC: 74 AN: 4820

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00542 AC: 369 AN: 68032

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.00430 Hom.: 0

Bravo AF: 0.00475

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.00752

EpiControl AF: 0.00569

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		0.021
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs76484258; hg19: chr7-106799958;