6-122557691-A-G

Variant names:

• chr6-122557691-A-G
• rs197687
• ENST00000392491.6:c.-247-28230A>G

Variant summary

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

The NM_001270394.2(PKIB):​c.-287-28230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,044 control chromosomes in the GnomAD database, including 32,003 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 0.64 (32003 hom., cov: 32)
• Consequence: PKIB NM_001270394.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270394.2. 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
	PKIB	NM_001270394.2		c.-287-28230A>G		intron	N/A	NP_001257323.1
	PKIB	NM_001270393.2		c.-247-28230A>G		intron	N/A	NP_001257322.1
	PKIB	NM_181794.3		c.-247-28230A>G		intron	N/A	NP_861459.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKIB	ENST00000392491.6	TSL:1	c.-247-28230A>G		intron	N/A	ENSP00000376281.1
	PKIB	ENST00000615438.4	TSL:5	c.-287-28230A>G		intron	N/A	ENSP00000480824.1
	PKIB	ENST00000583007.2	TSL:5	n.180-24074A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97918 AN: 151928 Hom.: 32002 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.644 AC: 97944 AN: 152044 Hom.: 32003 Cov.: 32 AF XY: 0.651 AC XY: 48358 AN XY: 74326

African (AFR) AF: 0.552 AC: 22874 AN: 41456

American (AMR) AF: 0.750 AC: 11454 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2387 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3012 AN: 5168

South Asian (SAS) AF: 0.830 AC: 3997 AN: 4814

European-Finnish (FIN) AF: 0.669 AC: 7080 AN: 10582

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.662 AC: 44972 AN: 67958

Other (OTH) AF: 0.647 AC: 1368 AN: 2114

Alfa AF: 0.666 Hom.: 5892

Bravo AF: 0.640

Asia WGS AF: 0.693 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.57
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: rs197687; hg19: chr6-122878836;