1-84156830-G-T

Variant names:

• chr1-84156830-G-T
• rs903263
• NM_182948.4:c.187+12282G>T

Variant summary

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

The NM_182948.4(PRKACB):​c.187+12282G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,850 control chromosomes in the GnomAD database, including 18,727 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 0.49 (18727 hom., cov: 32)
• Consequence: PRKACB NM_182948.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182948.4. 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_182948.4	MANE Select	c.187+12282G>T		intron	N/A	NP_891993.1
	PRKACB	NM_002731.4		c.47-22347G>T		intron	N/A	NP_002722.1
	PRKACB	NM_001300916.2		c.187+12282G>T		intron	N/A	NP_001287845.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	ENST00000370685.7	TSL:1 MANE Select	c.187+12282G>T		intron	N/A	ENSP00000359719.3
	PRKACB	ENST00000370689.6	TSL:1	c.47-22347G>T		intron	N/A	ENSP00000359723.2
	PRKACB	ENST00000370688.7	TSL:1	c.47-22347G>T		intron	N/A	ENSP00000359722.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74224 AN: 151736 Hom.: 18700 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.489 AC: 74279 AN: 151850 Hom.: 18727 Cov.: 32 AF XY: 0.484 AC XY: 35895 AN XY: 74192

African (AFR) AF: 0.412 AC: 17047 AN: 41396

American (AMR) AF: 0.426 AC: 6505 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3472

East Asian (EAS) AF: 0.367 AC: 1893 AN: 5156

South Asian (SAS) AF: 0.384 AC: 1845 AN: 4804

European-Finnish (FIN) AF: 0.510 AC: 5380 AN: 10542

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38255 AN: 67910

Other (OTH) AF: 0.499 AC: 1053 AN: 2112

Alfa AF: 0.535 Hom.: 83015

Bravo AF: 0.480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs903263; hg19: chr1-84622513; COSMIC: COSV65768842;