rs2230033

chr21-38299554-G-A

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 (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/exons	MANE	UniProt
KCNJ15	NM_170736.3	c.293G>A	p.Gly98Asp	missense_variant	3/3	ENST00000398938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ15	ENST00000398938.7	c.293G>A	p.Gly98Asp	missense_variant	3/3	1	NM_170736.3	P1

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

GnomAD3 exomes AF: 0.454 AC: 114169 AN: 251468 Hom.: 27803 AF XY: 0.459 AC XY: 62368 AN XY: 135912

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 SAS exome AF: 0.374

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

Gnomad4 AFR exome AF: 0.0869

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.489

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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.400

Alfa AF: 0.509 Hom.: 50445

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
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;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.29	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

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