rs2836246

Positions:

• chr21-38256276-T-C

Variant summary

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

The NM_001276437.2(KCNJ15):​c.-198-828T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 150,978 control chromosomes in the GnomAD database, including 2,277 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 0.10 (2277 hom., cov: 27)
• Consequence: KCNJ15 NM_001276437.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ15	NM_001276437.2	c.-198-828T>C		intron_variant
KCNJ15	NM_001276438.2	c.-117+26253T>C		intron_variant
KCNJ15	NM_001276439.2	c.-256-770T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ15	ENST00000547341.5	c.-398-770T>C		intron_variant		3
KCNJ15	ENST00000547595.5	c.-116-40650T>C		intron_variant		2
KCNJ15	ENST00000548700.5	c.-107-40650T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15714 AN: 150864 Hom.: 2272 Cov.: 27

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.00966

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.104 AC: 15739 AN: 150978 Hom.: 2277 Cov.: 27 AF XY: 0.0990 AC XY: 7307 AN XY: 73776

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.000777

Gnomad4 SAS AF: 0.0470

Gnomad4 FIN AF: 0.00966

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0804

Alfa AF: 0.0424 Hom.: 567

Bravo AF: 0.115

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0040
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2836246; hg19: chr21-39628198;