rs12405120

Positions:

• chr1-84090840-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+12469T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,962 control chromosomes in the GnomAD database, including 12,326 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 0.38 (12326 hom., cov: 31)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_001375576.1	c.46+12469T>C		intron_variant
PRKACB	NM_002731.4	c.46+12469T>C		intron_variant
PRKACB	NM_207578.3	c.46+12469T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370688.7	c.46+12469T>C		intron_variant		1
PRKACB	ENST00000370689.6	c.46+12469T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58277 AN: 151842 Hom.: 12321 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.384 AC: 58289 AN: 151962 Hom.: 12326 Cov.: 31 AF XY: 0.380 AC XY: 28223 AN XY: 74292

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.398

Alfa AF: 0.419 Hom.: 2484

Bravo AF: 0.370

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12405120; hg19: chr1-84556523;