rs1057738

Positions:

• chr1-84205133-A-C

Variant summary

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

The NM_001300916.2(PRKACB):​c.*643A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 979,392 control chromosomes in the GnomAD database, including 141,207 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 0.43 (15926 hom., cov: 32)
  • Exomes 𝑓: 0.55 (125281 hom.)
• Consequence: PRKACB NM_001300916.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

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]

PRKACB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKACB	NM_182948.4	c.906+2328A>C		intron_variant		ENST00000370685.7	NP_891993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370685.7	c.906+2328A>C		intron_variant		1	NM_182948.4	ENSP00000359719.3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65892 AN: 151554 Hom.: 15925 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.466

GnomAD4 exome AF: 0.546 AC: 452264 AN: 827722 Hom.: 125281 Cov.: 26 AF XY: 0.547 AC XY: 209236 AN XY: 382458

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.434 AC: 65891 AN: 151670 Hom.: 15926 Cov.: 32 AF XY: 0.430 AC XY: 31841 AN XY: 74054

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.562

Gnomad4 OTH AF: 0.463

Alfa AF: 0.506 Hom.: 6262

Bravo AF: 0.418

Asia WGS AF: 0.356 AC: 1235 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057738; hg19: chr1-84670816; COSMIC: COSV65759181; COSMIC: COSV65759181;