rs12129768

Variant names:

• chr1-84162972-T-C
• rs12129768
• NM_182948.4:c.188-16205T>C

Variant summary

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

The NM_182948.4(PRKACB):​c.188-16205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,214 control chromosomes in the GnomAD database, including 695 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 0.080 (695 hom., cov: 32)
• Consequence: PRKACB NM_182948.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• Publications: 6 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 = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_182948.4	c.188-16205T>C		intron_variant	Intron 1 of 9	ENST00000370685.7	NP_891993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370685.7	c.188-16205T>C		intron_variant	Intron 1 of 9	1	NM_182948.4	ENSP00000359719.3
PRKACB	ENST00000370689.6	c.47-16205T>C		intron_variant	Intron 1 of 9	1		ENSP00000359723.2
PRKACB	ENST00000370688.7	c.47-16205T>C		intron_variant	Intron 1 of 8	1		ENSP00000359722.3
PRKACB	ENST00000470673.5	n.298+5567T>C		intron_variant	Intron 2 of 6	3

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12213 AN: 152096 Hom.: 694 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0802 AC: 12209 AN: 152214 Hom.: 695 Cov.: 32 AF XY: 0.0796 AC XY: 5927 AN XY: 74418

African (AFR) AF: 0.0217 AC: 904 AN: 41568

American (AMR) AF: 0.0912 AC: 1392 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3470

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5176

South Asian (SAS) AF: 0.0442 AC: 213 AN: 4822

European-Finnish (FIN) AF: 0.124 AC: 1319 AN: 10596

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7682 AN: 68002

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.103 Hom.: 453

Bravo AF: 0.0783

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		0.18
Mutation Taster		=99/1	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: rs12129768; hg19: chr1-84628655;