1-84204901-T-A

Position:

• chr1-84204901-T-A

Variant summary

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

The ENST00000370680.5(PRKACB):​c.*411T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 978,266 control chromosomes in the GnomAD database, including 145,265 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 0.49 (18730 hom., cov: 32)
  • Exomes 𝑓: 0.55 (126535 hom.)
• Consequence: PRKACB ENST00000370680.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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 = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_182948.4	c.906+2096T>A		intron_variant		ENST00000370685.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370685.7	c.906+2096T>A		intron_variant		1	NM_182948.4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74139 AN: 151512 Hom.: 18699 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.551 AC: 455762 AN: 826636 Hom.: 126535 Cov.: 23 AF XY: 0.551 AC XY: 210654 AN XY: 381986

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.525

GnomAD4 genome AF: 0.489 AC: 74200 AN: 151630 Hom.: 18730 Cov.: 32 AF XY: 0.484 AC XY: 35870 AN XY: 74076

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.498

Alfa AF: 0.528 Hom.: 2652

Bravo AF: 0.480

Asia WGS AF: 0.384 AC: 1327 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.46

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: rs10782824; hg19: chr1-84670584; COSMIC: COSV65759178; COSMIC: COSV65759178;