rs2836246

Variant names:

• chr21-38256276-T-C
• rs2836246
• NM_001276437.2:c.-198-828T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNJ15	NM_001276437.2	c.-198-828T>C		intron_variant	Intron 1 of 3		NP_001263366.1
KCNJ15	NM_001276438.2	c.-117+26253T>C		intron_variant	Intron 1 of 2		NP_001263367.1
KCNJ15	NM_001276439.2	c.-256-770T>C		intron_variant	Intron 1 of 3		NP_001263368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000547341.5	c.-398-770T>C		intron_variant	Intron 1 of 4	3		ENSP00000447111.1
KCNJ15	ENST00000547595.5	c.-116-40650T>C		intron_variant	Intron 1 of 2	2		ENSP00000450254.1
KCNJ15	ENST00000548700.5	c.-107-40650T>C		intron_variant	Intron 1 of 2	3		ENSP00000448886.1

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

African (AFR) AF: 0.324 AC: 13177 AN: 40718

American (AMR) AF: 0.0422 AC: 642 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3464

East Asian (EAS) AF: 0.000777 AC: 4 AN: 5148

South Asian (SAS) AF: 0.0470 AC: 226 AN: 4812

European-Finnish (FIN) AF: 0.00966 AC: 101 AN: 10460

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1379 AN: 67866

Other (OTH) AF: 0.0804 AC: 169 AN: 2102

Alfa AF: 0.0523 Hom.: 1016

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
PhyloP100		-1.8
PromoterAI		-0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2836246; hg19: chr21-39628198;