6-122638360-G-C

Variant names:

• chr6-122638360-G-C
• rs17084680
• NM_181795.3:c.-76+4993G>C

Variant summary

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

The NM_181795.3(PKIB):​c.-76+4993G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,064 control chromosomes in the GnomAD database, including 5,477 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 0.26 (5477 hom., cov: 32)
• Consequence: PKIB NM_181795.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 2 publications found

Genes affected

PKIB (HGNC:9018): (cAMP-dependent protein kinase inhibitor beta) This gene encodes a member of the cAMP-dependent protein kinase inhibitor family. The encoded protein may play a role in the protein kinase A (PKA) pathway by interacting with the catalytic subunit of PKA, and overexpression of this gene may play a role in prostate cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKIB	NM_181795.3	c.-76+4993G>C		intron_variant	Intron 2 of 4	ENST00000368452.7	NP_861460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKIB	ENST00000368452.7	c.-76+4993G>C		intron_variant	Intron 2 of 4	1	NM_181795.3	ENSP00000357437.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38897 AN: 151946 Hom.: 5476 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.256 AC: 38908 AN: 152064 Hom.: 5477 Cov.: 32 AF XY: 0.256 AC XY: 19060 AN XY: 74334

African (AFR) AF: 0.146 AC: 6056 AN: 41486

American (AMR) AF: 0.238 AC: 3644 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2033 AN: 5162

South Asian (SAS) AF: 0.187 AC: 902 AN: 4820

European-Finnish (FIN) AF: 0.313 AC: 3310 AN: 10568

Middle Eastern (MID) AF: 0.241 AC: 70 AN: 290

European-Non Finnish (NFE) AF: 0.309 AC: 21013 AN: 67970

Other (OTH) AF: 0.239 AC: 502 AN: 2104

Alfa AF: 0.172 Hom.: 386

Bravo AF: 0.250

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.65
PhyloP100		-0.41
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: rs17084680; hg19: chr6-122959505; COSMIC: COSV63761423;