chr6-122576135-C-G

Variant names:

• chr6-122576135-C-G
• rs9398678
• ENST00000392491.6:c.-247-9786C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270394.2(PKIB):​c.-287-9786C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,204 control chromosomes in the GnomAD database, including 1,232 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 0.11 (1232 hom., cov: 31)
• Consequence: PKIB NM_001270394.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.173

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]

ENSG00000287258 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKIB	NM_001270394.2	c.-287-9786C>G		intron_variant	Intron 2 of 7		NP_001257323.1
PKIB	NM_001270393.2	c.-247-9786C>G		intron_variant	Intron 3 of 7		NP_001257322.1
PKIB	NM_181794.3	c.-247-9786C>G		intron_variant	Intron 2 of 6		NP_861459.1
PKIB	XM_047419002.1	c.-4076-5630C>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.-247-9786C>G		intron_variant	Intron 2 of 6	1		ENSP00000376281.1
PKIB	ENST00000615438.4	c.-287-9786C>G		intron_variant	Intron 2 of 7	5		ENSP00000480824.1
PKIB	ENST00000583007.2	n.180-5630C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17229 AN: 152086 Hom.: 1230 Cov.: 31

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.113 AC: 17232 AN: 152204 Hom.: 1232 Cov.: 31 AF XY: 0.108 AC XY: 8059 AN XY: 74402

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0651 Hom.: 80

Bravo AF: 0.113

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.41

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: rs9398678; hg19: chr6-122897280;