rs1402694

Variant names:

• chr1-84134830-C-T
• rs1402694
• ENST00000370689.6:c.47-44347C>T

Variant summary

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

The ENST00000370689.6(PRKACB):​c.47-44347C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,962 control chromosomes in the GnomAD database, including 17,739 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 0.47 (17739 hom., cov: 32)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 2 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_002731.4	c.47-44347C>T		intron_variant	Intron 1 of 9		NP_002722.1
PRKACB	NM_001375576.1	c.47-44347C>T		intron_variant	Intron 1 of 8		NP_001362505.1
PRKACB	NM_207578.3	c.47-44347C>T		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.47-44347C>T		intron_variant	Intron 1 of 9	1		ENSP00000359723.2
PRKACB	ENST00000370688.7	c.47-44347C>T		intron_variant	Intron 1 of 8	1		ENSP00000359722.3

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71857 AN: 151844 Hom.: 17721 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.473 AC: 71897 AN: 151962 Hom.: 17739 Cov.: 32 AF XY: 0.468 AC XY: 34732 AN XY: 74268

African (AFR) AF: 0.371 AC: 15390 AN: 41444

American (AMR) AF: 0.415 AC: 6343 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1866 AN: 5164

South Asian (SAS) AF: 0.363 AC: 1747 AN: 4810

European-Finnish (FIN) AF: 0.513 AC: 5410 AN: 10556

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.558 AC: 37878 AN: 67918

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.507 Hom.: 3115

Bravo AF: 0.462

Asia WGS AF: 0.365 AC: 1269 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.34
PhyloP100		-1.9
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: rs1402694; hg19: chr1-84600513; COSMIC: COSV65771875;