rs12728744

Positions:

• chr1-84116872-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000370689.6(PRKACB):​c.46+38501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 152,248 control chromosomes in the GnomAD database, including 104 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 0.029 (104 hom., cov: 32)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0289 (4403/152248) while in subpopulation NFE AF= 0.0415 (2820/68008). AF 95% confidence interval is 0.0402. There are 104 homozygotes in gnomad4. There are 2230 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4403 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_001375576.1	c.46+38501A>G		intron_variant
PRKACB	NM_002731.4	c.46+38501A>G		intron_variant
PRKACB	NM_207578.3	c.46+38501A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370688.7	c.46+38501A>G		intron_variant		1
PRKACB	ENST00000370689.6	c.46+38501A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4402 AN: 152130 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.00644

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.0864

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0196

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

GnomAD4 genome AF: 0.0289 AC: 4403 AN: 152248 Hom.: 104 Cov.: 32 AF XY: 0.0300 AC XY: 2230 AN XY: 74434

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.0864

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0352 Hom.: 49

Bravo AF: 0.0231

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12728744; hg19: chr1-84582555;