6-122703064-A-G

Variant names:

• chr6-122703064-A-G
• rs17084747
• NM_181795.3:c.-8-14723A>G

Variant summary

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

The NM_181795.3(PKIB):​c.-8-14723A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,264 control chromosomes in the GnomAD database, including 392 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 0.062 (392 hom., cov: 32)
• Consequence: PKIB NM_181795.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKIB	NM_181795.3	c.-8-14723A>G		intron_variant	Intron 3 of 4	ENST00000368452.7	NP_861460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKIB	ENST00000368452.7	c.-8-14723A>G		intron_variant	Intron 3 of 4	1	NM_181795.3	ENSP00000357437.2

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9367 AN: 152146 Hom.: 390 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0703

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0616 AC: 9373 AN: 152264 Hom.: 392 Cov.: 32 AF XY: 0.0597 AC XY: 4445 AN XY: 74450

African (AFR) AF: 0.0170 AC: 707 AN: 41582

American (AMR) AF: 0.0704 AC: 1076 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.134 AC: 694 AN: 5182

South Asian (SAS) AF: 0.0689 AC: 332 AN: 4820

European-Finnish (FIN) AF: 0.0603 AC: 639 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5430 AN: 68000

Other (OTH) AF: 0.0719 AC: 152 AN: 2114

Alfa AF: 0.0673 Hom.: 312

Bravo AF: 0.0636

Asia WGS AF: 0.0890 AC: 309 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		0.35
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: rs17084747; hg19: chr6-123024209;