1-84235568-T-C

Position:

• chr1-84235568-T-C

Variant summary

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

The NM_182948.4(PRKACB):​c.*263T>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 0.807 in 353,676 control chromosomes in the GnomAD database, including 115,096 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 0.81 (50334 hom., cov: 32)
  • Exomes 𝑓: 0.80 (64762 hom.)
• Consequence: PRKACB NM_182948.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKACB	NM_182948.4	c.*263T>C		3_prime_UTR_variant	10/10	ENST00000370685.7	NP_891993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370685.7	c.*263T>C		3_prime_UTR_variant	10/10	1	NM_182948.4	ENSP00000359719.3

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123557 AN: 152072 Hom.: 50292 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.802 AC: 161616 AN: 201486 Hom.: 64762 Cov.: 3 AF XY: 0.796 AC XY: 82916 AN XY: 104108

Gnomad4 AFR exome AF: 0.836

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.809

Gnomad4 EAS exome AF: 0.845

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.804

Gnomad4 OTH exome AF: 0.814

GnomAD4 genome AF: 0.812 AC: 123640 AN: 152190 Hom.: 50334 Cov.: 32 AF XY: 0.813 AC XY: 60508 AN XY: 74418

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.813

Alfa AF: 0.805 Hom.: 48897

Bravo AF: 0.814

Asia WGS AF: 0.730 AC: 2539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.5
DANN	Benign	0.73

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: rs600674; hg19: chr1-84701251;