6-122557691-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKIB	NM_001270394.2	c.-287-28230A>G		intron_variant	Intron 2 of 7		NP_001257323.1
PKIB	NM_001270393.2	c.-247-28230A>G		intron_variant	Intron 3 of 7		NP_001257322.1
PKIB	NM_181794.3	c.-247-28230A>G		intron_variant	Intron 2 of 6		NP_861459.1
PKIB	XM_047419002.1	c.-4076-24074A>G		intron_variant	Intron 2 of 8		XP_047274958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKIB	ENST00000392491.6	c.-247-28230A>G		intron_variant	Intron 2 of 6	1		ENSP00000376281.1
PKIB	ENST00000615438.4	c.-287-28230A>G		intron_variant	Intron 2 of 7	5		ENSP00000480824.1
PKIB	ENST00000583007.2	n.180-24074A>G		intron_variant	Intron 1 of 3	5

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

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.669

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.647

Alfa AF: 0.670 Hom.: 5766

Bravo AF: 0.640

Asia WGS AF: 0.693 AC: 2407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs197687; hg19: chr6-122878836;