rs12129768

chr1-84162972-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.188-16205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,214 control chromosomes in the GnomAD database, including 695 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 0.080 (695 hom., cov: 32)
• Consequence: PRKACB NM_182948.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_182948.4	c.188-16205T>C		intron_variant		ENST00000370685.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370685.7	c.188-16205T>C		intron_variant		1	NM_182948.4
PRKACB	ENST00000370688.7	c.47-16205T>C		intron_variant		1
PRKACB	ENST00000370689.6	c.47-16205T>C		intron_variant		1		P1
PRKACB	ENST00000470673.5	n.298+5567T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12213 AN: 152096 Hom.: 694 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0802 AC: 12209 AN: 152214 Hom.: 695 Cov.: 32 AF XY: 0.0796 AC XY: 5927 AN XY: 74418

Gnomad4 AFR AF: 0.0217

Gnomad4 AMR AF: 0.0912

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0442

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.102 Hom.: 411

Bravo AF: 0.0783

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.8
Dann	Benign	0.53

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: rs12129768; hg19: chr1-84628655;