rs1565823

Variant names:

• chr1-84110937-G-A
• rs1565823
• ENST00000370689.6:c.46+32566G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370689.6(PRKACB):​c.46+32566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,670 control chromosomes in the GnomAD database, including 15,335 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 0.42 (15335 hom., cov: 31)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• Publications: 3 publications found

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]

PRKACB Gene-Disease associations (from GenCC):

• cardioacrofacial dysplasia 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_002731.4	c.46+32566G>A		intron_variant	Intron 1 of 9		NP_002722.1
PRKACB	NM_001375576.1	c.46+32566G>A		intron_variant	Intron 1 of 8		NP_001362505.1
PRKACB	NM_207578.3	c.46+32566G>A		intron_variant	Intron 1 of 8		NP_997461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370689.6	c.46+32566G>A		intron_variant	Intron 1 of 9	1		ENSP00000359723.2
PRKACB	ENST00000370688.7	c.46+32566G>A		intron_variant	Intron 1 of 8	1		ENSP00000359722.3

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63833 AN: 151552 Hom.: 15337 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.421 AC: 63824 AN: 151670 Hom.: 15335 Cov.: 31 AF XY: 0.417 AC XY: 30890 AN XY: 74092

African (AFR) AF: 0.193 AC: 7981 AN: 41418

American (AMR) AF: 0.400 AC: 6080 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1722 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1766 AN: 5142

South Asian (SAS) AF: 0.356 AC: 1708 AN: 4802

European-Finnish (FIN) AF: 0.513 AC: 5401 AN: 10524

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37728 AN: 67796

Other (OTH) AF: 0.446 AC: 940 AN: 2106

Alfa AF: 0.499 Hom.: 10678

Bravo AF: 0.403

Asia WGS AF: 0.341 AC: 1186 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.29
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1565823; hg19: chr1-84576620; COSMIC: COSV65771811;