rs12563929

chr1-84082601-T-C

Variant summary

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

The ENST00000370689.6(PRKACB):c.46+4230T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 152,282 control chromosomes in the GnomAD database, including 235 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 0.048 (235 hom., cov: 32)
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_001375576.1	c.46+4230T>C		intron_variant
PRKACB	NM_002731.4	c.46+4230T>C		intron_variant
PRKACB	NM_207578.3	c.46+4230T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370688.7	c.46+4230T>C		intron_variant		1
PRKACB	ENST00000370689.6	c.46+4230T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7306 AN: 152164 Hom.: 236 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0779

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0479 AC: 7297 AN: 152282 Hom.: 235 Cov.: 32 AF XY: 0.0473 AC XY: 3522 AN XY: 74460

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.0779

Gnomad4 EAS AF: 0.0920

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0663 Hom.: 457

Bravo AF: 0.0452

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.9
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12563929; hg19: chr1-84548284;