rs1402694

Positions:

• chr1-84134830-C-T

Variant summary

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

The ENST00000370689.6(PRKACB):​c.47-44347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,962 control chromosomes in the GnomAD database, including 17,739 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 0.47 (17739 hom., cov: 32)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKACB	NM_001375576.1	c.47-44347C>T		intron_variant			NP_001362505.1
PRKACB	NM_002731.4	c.47-44347C>T		intron_variant			NP_002722.1
PRKACB	NM_207578.3	c.47-44347C>T		intron_variant			NP_997461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370688.7	c.47-44347C>T		intron_variant		1		ENSP00000359722
PRKACB	ENST00000370689.6	c.47-44347C>T		intron_variant		1		ENSP00000359723	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71857 AN: 151844 Hom.: 17721 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.473 AC: 71897 AN: 151962 Hom.: 17739 Cov.: 32 AF XY: 0.468 AC XY: 34732 AN XY: 74268

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.482

Alfa AF: 0.511 Hom.: 3044

Bravo AF: 0.462

Asia WGS AF: 0.365 AC: 1269 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1402694; hg19: chr1-84600513; COSMIC: COSV65771875;