7-107070321-G-A

Variant names:

• chr7-107070321-G-A
• rs3729869
• NM_002736.3:c.343+5G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_002736.3(PRKAR2B):​c.343+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00354 in 1,599,534 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (93 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (59 hom.)
• Consequence: PRKAR2B NM_002736.3 splice_region, intron
• Scores: Splicing: ADA: 0.6660
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.96
• Publications: 3 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]

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 7-107070321-G-A is Benign according to our data. Variant chr7-107070321-G-A is described in ClinVar as Benign. ClinVar VariationId is 780702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0596 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	NM_002736.3	MANE Select	c.343+5G>A		splice_region intron	N/A	NP_002727.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR2B	ENST00000265717.5	TSL:1 MANE Select	c.343+5G>A		splice_region intron	N/A	ENSP00000265717.4	P31323
	PRKAR2B	ENST00000854598.1		c.343+5G>A		splice_region intron	N/A	ENSP00000524657.1
	PRKAR2B	ENST00000913925.1		c.343+5G>A		splice_region intron	N/A	ENSP00000583984.1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2783 AN: 152142 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00955

GnomAD2 exomes AF: 0.00529 AC: 1318 AN: 249174 AF XY: 0.00396

Gnomad AFR exome AF: 0.0649

Gnomad AMR exome AF: 0.00470

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000548

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00198 AC: 2872 AN: 1447274 Hom.: 59 Cov.: 28 AF XY: 0.00180 AC XY: 1294 AN XY: 720706

African (AFR) AF: 0.0568 AC: 1873 AN: 33004

American (AMR) AF: 0.00515 AC: 228 AN: 44290

Ashkenazi Jewish (ASJ) AF: 0.00150 AC: 39 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52652

Middle Eastern (MID) AF: 0.00383 AC: 22 AN: 5740

European-Non Finnish (NFE) AF: 0.000382 AC: 421 AN: 1100802

Other (OTH) AF: 0.00462 AC: 277 AN: 59894

GnomAD4 genome AF: 0.0183 AC: 2788 AN: 152260 Hom.: 93 Cov.: 32 AF XY: 0.0180 AC XY: 1341 AN XY: 74440

African (AFR) AF: 0.0616 AC: 2557 AN: 41540

American (AMR) AF: 0.0109 AC: 166 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68022

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.00777 Hom.: 62

Bravo AF: 0.0209

Asia WGS AF: 0.00520 AC: 18 AN: 3476

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	-0.25
CADD	Uncertain	24
DANN	Benign	0.95
PhyloP100		5.0
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.67
dbscSNV1_RF	Benign	0.53
SpliceAI score (max)		0.040		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: rs3729869; hg19: chr7-106710766;