rs10493750

Variant names:

• chr1-84096582-A-G
• rs10493750
• ENST00000370689.6:c.46+18211A>G

Variant summary

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

The ENST00000370689.6(PRKACB):​c.46+18211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,008 control chromosomes in the GnomAD database, including 13,279 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 0.41 (13279 hom., cov: 33)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_002731.4	c.46+18211A>G		intron_variant	Intron 1 of 9		NP_002722.1
PRKACB	NM_001375576.1	c.46+18211A>G		intron_variant	Intron 1 of 8		NP_001362505.1
PRKACB	NM_207578.3	c.46+18211A>G		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+18211A>G		intron_variant	Intron 1 of 9	1		ENSP00000359723.2
PRKACB	ENST00000370688.7	c.46+18211A>G		intron_variant	Intron 1 of 8	1		ENSP00000359722.3

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61743 AN: 151890 Hom.: 13271 Cov.: 33

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.406 AC: 61772 AN: 152008 Hom.: 13279 Cov.: 33 AF XY: 0.402 AC XY: 29869 AN XY: 74318

African (AFR) AF: 0.293 AC: 12139 AN: 41476

American (AMR) AF: 0.382 AC: 5833 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1450 AN: 3464

East Asian (EAS) AF: 0.271 AC: 1400 AN: 5172

South Asian (SAS) AF: 0.306 AC: 1477 AN: 4830

European-Finnish (FIN) AF: 0.466 AC: 4927 AN: 10582

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33233 AN: 67912

Other (OTH) AF: 0.413 AC: 869 AN: 2106

Alfa AF: 0.446 Hom.: 9246

Bravo AF: 0.396

Asia WGS AF: 0.291 AC: 1015 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	2.9
DANN	Benign	0.72
PhyloP100		0.16
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: rs10493750; hg19: chr1-84562265; COSMIC: COSV65771796;