rs10493750

Positions:

• chr1-84096582-A-G

Variant summary

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

The ENST00000370689.6(PRKACB):​c.46+18211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,008 control chromosomes in the GnomAD database, including 13,279 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 0.41 (13279 hom., cov: 33)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

Genes affected

PRKACB (HGNC:9381): (protein kinase cAMP-activated catalytic subunit beta) The protein encoded by this gene is a member of the serine/threonine protein kinase family. The encoded protein is a catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase, which mediates signalling though cAMP. cAMP signaling is important to a number of processes, including cell proliferaton and differentiation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_001375576.1	c.46+18211A>G		intron_variant
PRKACB	NM_002731.4	c.46+18211A>G		intron_variant
PRKACB	NM_207578.3	c.46+18211A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370688.7	c.46+18211A>G		intron_variant		1
PRKACB	ENST00000370689.6	c.46+18211A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61743 AN: 151890 Hom.: 13271 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.406 AC: 61772 AN: 152008 Hom.: 13279 Cov.: 33 AF XY: 0.402 AC XY: 29869 AN XY: 74318

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.413

Alfa AF: 0.445 Hom.: 8333

Bravo AF: 0.396

Asia WGS AF: 0.291 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10493750; hg19: chr1-84562265; COSMIC: COSV65771796;