rs2065306

Variant names:

• chr21-38307523-C-G
• rs2065306
• NM_170736.3:c.*7134C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170736.3(KCNJ15):​c.*7134C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,034 control chromosomes in the GnomAD database, including 2,166 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 (2166 hom., cov: 32)
• Consequence: KCNJ15 NM_170736.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.*7134C>G		downstream_gene_variant		ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.*7134C>G		downstream_gene_variant		1	NM_170736.3	ENSP00000381911.2
KCNJ15	ENST00000328656.8	c.*7134C>G		downstream_gene_variant		1		ENSP00000331698.3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15249 AN: 151920 Hom.: 2163 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.00871

Gnomad OTH AF: 0.0854

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

GnomAD4 genome AF: 0.101 AC: 15286 AN: 152034 Hom.: 2166 Cov.: 32 AF XY: 0.0980 AC XY: 7280 AN XY: 74314

African (AFR) AF: 0.317 AC: 13135 AN: 41438

American (AMR) AF: 0.0423 AC: 647 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.0961 AC: 497 AN: 5174

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.0176 AC: 186 AN: 10550

Middle Eastern (MID) AF: 0.0483 AC: 14 AN: 290

European-Non Finnish (NFE) AF: 0.00871 AC: 592 AN: 67988

Other (OTH) AF: 0.0836 AC: 176 AN: 2106

Alfa AF: 0.0618 Hom.: 166

Bravo AF: 0.113

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.30
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs2065306; hg19: chr21-39679445;