rs2230033

Variant names:

• chr21-38299554-G-A
• rs2230033
• NM_170736.3:c.293G>A

Variant summary

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

The NM_170736.3(KCNJ15):​c.293G>A​(p.Gly98Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,613,712 control chromosomes in the GnomAD database, including 219,185 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G98C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.40 (14697 hom., cov: 31)
  • Exomes 𝑓: 0.52 (204488 hom.)
• Consequence: KCNJ15 NM_170736.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 48 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 (MetaRNN=2.3838878E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.293G>A	p.Gly98Asp	missense_variant	Exon 3 of 3	ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.293G>A	p.Gly98Asp	missense_variant	Exon 3 of 3	1	NM_170736.3	ENSP00000381911.2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60122 AN: 151818 Hom.: 14699 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.401

GnomAD2 exomes AF: 0.454 AC: 114169 AN: 251468 AF XY: 0.459

Gnomad AFR exome AF: 0.0971

Gnomad AMR exome AF: 0.451

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.288

Gnomad FIN exome AF: 0.491

Gnomad NFE exome AF: 0.544

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.520 AC: 760047 AN: 1461776 Hom.: 204488 Cov.: 51 AF XY: 0.517 AC XY: 375863 AN XY: 727204

African (AFR) AF: 0.0869 AC: 2910 AN: 33480

American (AMR) AF: 0.449 AC: 20081 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 12820 AN: 26136

East Asian (EAS) AF: 0.293 AC: 11625 AN: 39700

South Asian (SAS) AF: 0.377 AC: 32510 AN: 86258

European-Finnish (FIN) AF: 0.489 AC: 26145 AN: 53420

Middle Eastern (MID) AF: 0.423 AC: 2439 AN: 5766

European-Non Finnish (NFE) AF: 0.559 AC: 621975 AN: 1111902

Other (OTH) AF: 0.489 AC: 29542 AN: 60390

GnomAD4 genome AF: 0.396 AC: 60125 AN: 151936 Hom.: 14697 Cov.: 31 AF XY: 0.393 AC XY: 29196 AN XY: 74216

African (AFR) AF: 0.107 AC: 4434 AN: 41476

American (AMR) AF: 0.451 AC: 6882 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1698 AN: 3466

East Asian (EAS) AF: 0.288 AC: 1485 AN: 5148

South Asian (SAS) AF: 0.376 AC: 1803 AN: 4798

European-Finnish (FIN) AF: 0.495 AC: 5212 AN: 10522

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37343 AN: 67952

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.493 Hom.: 64884

Bravo AF: 0.380

TwinsUK AF: 0.562 AC: 2085

ALSPAC AF: 0.542 AC: 2089

ESP6500AA AF: 0.121 AC: 533

ESP6500EA AF: 0.547 AC: 4707

ExAC AF: 0.446 AC: 54135

Asia WGS AF: 0.318 AC: 1110 AN: 3478

EpiCase AF: 0.540

EpiControl AF: 0.532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	5.7
DANN	Benign	0.12
DEOGEN2	Benign	0.19	T;T;T;T;T;T;.;T;T;T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.42	.;T;.;.;.;.;T;.;.;T;T
MetaRNN	Benign	0.00024	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.74	N;N;.;N;N;N;.;N;N;.;.
PhyloP100		1.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.85	.;.;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.28
Sift	Benign	0.62	.;.;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.62	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.093	B;B;.;B;B;B;.;B;B;.;.
Vest4		0.051
MPC		0.58
ClinPred		0.016	T
GERP RS		4.2
Varity_R		0.061
gMVP		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2230033; hg19: chr21-39671476; COSMIC: COSV60810220; COSMIC: COSV60810220;