rs2836266

Positions:

• chr21-38272691-T-C

Variant summary

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

The NM_170736.3(KCNJ15):​c.-117+15506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,150 control chromosomes in the GnomAD database, including 3,058 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 0.19 (3058 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KCNJ15 NM_170736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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 -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 = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ15	NM_170736.3	c.-117+15506T>C		intron_variant		ENST00000398938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ15	ENST00000398938.7	c.-117+15506T>C		intron_variant		1	NM_170736.3	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28529 AN: 152030 Hom.: 3051 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.161

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.188 AC: 28541 AN: 152150 Hom.: 3058 Cov.: 33 AF XY: 0.193 AC XY: 14337 AN XY: 74380

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.160

Alfa AF: 0.187 Hom.: 344

Bravo AF: 0.182

Asia WGS AF: 0.392 AC: 1365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.81

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: rs2836266; hg19: chr21-39644613;