chr21-38299525-C-T

Position:

• chr21-38299525-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_170736.3(KCNJ15):​c.264C>T​(p.Ile88Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,088 control chromosomes in the GnomAD database, including 478 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 0.031 (176 hom., cov: 32)
  • Exomes 𝑓: 0.011 (302 hom.)
• Consequence: KCNJ15 NM_170736.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.081 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.264C>T	p.Ile88Ile	synonymous_variant	3/3	ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.264C>T	p.Ile88Ile	synonymous_variant	3/3	1	NM_170736.3	ENSP00000381911.2

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4751 AN: 152086 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0876

Gnomad SAS AF: 0.00353

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00745

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0199 AC: 5001 AN: 251476 Hom.: 168 AF XY: 0.0176 AC XY: 2396 AN XY: 135912

Gnomad AFR exome AF: 0.0837

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00377

Gnomad EAS exome AF: 0.0966

Gnomad SAS exome AF: 0.00526

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.00764

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0114 AC: 16719 AN: 1461884 Hom.: 302 Cov.: 32 AF XY: 0.0108 AC XY: 7826 AN XY: 727246

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.00333

Gnomad4 EAS exome AF: 0.0667

Gnomad4 SAS exome AF: 0.00589

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.00747

Gnomad4 OTH exome AF: 0.0176

GnomAD4 genome AF: 0.0312 AC: 4750 AN: 152204 Hom.: 176 Cov.: 32 AF XY: 0.0308 AC XY: 2290 AN XY: 74428

Gnomad4 AFR AF: 0.0799

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.00353

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.00745

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0194 Hom.: 35

Bravo AF: 0.0351

Asia WGS AF: 0.0330 AC: 116 AN: 3478

EpiCase AF: 0.00703

EpiControl AF: 0.00848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.52

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: rs3746876; hg19: chr21-39671447;