1-84090840-T-C

Variant names:

• chr1-84090840-T-C
• rs12405120
• ENST00000370689.6:c.46+12469T>C

Variant summary

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

The ENST00000370689.6(PRKACB):​c.46+12469T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,962 control chromosomes in the GnomAD database, including 12,326 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 0.38 (12326 hom., cov: 31)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370689.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	NM_002731.4		c.46+12469T>C		intron	N/A	NP_002722.1
	PRKACB	NM_001375576.1		c.46+12469T>C		intron	N/A	NP_001362505.1
	PRKACB	NM_207578.3		c.46+12469T>C		intron	N/A	NP_997461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	ENST00000370689.6	TSL:1	c.46+12469T>C		intron	N/A	ENSP00000359723.2
	PRKACB	ENST00000370688.7	TSL:1	c.46+12469T>C		intron	N/A	ENSP00000359722.3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58277 AN: 151842 Hom.: 12321 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.384 AC: 58289 AN: 151962 Hom.: 12326 Cov.: 31 AF XY: 0.380 AC XY: 28223 AN XY: 74292

African (AFR) AF: 0.215 AC: 8888 AN: 41414

American (AMR) AF: 0.374 AC: 5724 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3466

East Asian (EAS) AF: 0.271 AC: 1398 AN: 5160

South Asian (SAS) AF: 0.300 AC: 1442 AN: 4810

European-Finnish (FIN) AF: 0.465 AC: 4911 AN: 10562

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.489 AC: 33206 AN: 67952

Other (OTH) AF: 0.398 AC: 838 AN: 2108

Alfa AF: 0.415 Hom.: 2512

Bravo AF: 0.370

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		0.069
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: rs12405120; hg19: chr1-84556523;