1-84156830-G-T

Position:

• chr1-84156830-G-T

Variant summary

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

The NM_182948.4(PRKACB):​c.187+12282G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,850 control chromosomes in the GnomAD database, including 18,727 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 (18727 hom., cov: 32)
• Consequence: PRKACB NM_182948.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKACB	NM_182948.4	c.187+12282G>T		intron_variant		ENST00000370685.7	NP_891993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370685.7	c.187+12282G>T		intron_variant		1	NM_182948.4	ENSP00000359719
PRKACB	ENST00000370688.7	c.47-22347G>T		intron_variant		1		ENSP00000359722
PRKACB	ENST00000370689.6	c.47-22347G>T		intron_variant		1		ENSP00000359723	P1
PRKACB	ENST00000470673.5	n.228-505G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74224 AN: 151736 Hom.: 18700 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.489 AC: 74279 AN: 151850 Hom.: 18727 Cov.: 32 AF XY: 0.484 AC XY: 35895 AN XY: 74192

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.499

Alfa AF: 0.540 Hom.: 36735

Bravo AF: 0.480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.41

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: rs903263; hg19: chr1-84622513; COSMIC: COSV65768842;