Variant 21-38299277-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_170736.3(KCNJ15):c.16A>G(p.Ile6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,612,450 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 14 hom., cov: 33)

Exomes 𝑓: 0.011 ( 127 hom. )

Consequence

KCNJ15
NM_170736.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.224

Variant links:

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]

KCNJ15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032828748).

BP6

Variant 21-38299277-A-G is Benign according to our data. Variant chr21-38299277-A-G is described in ClinVar as [Benign]. Clinvar id is 770817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ15	NM_170736.3 linkuse as main transcript	c.16A>G	p.Ile6Val	missense_variant	3/3	ENST00000398938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ15	ENST00000398938.7 linkuse as main transcript	c.16A>G	p.Ile6Val	missense_variant	3/3	1	NM_170736.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00765

AC:

1164

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00854

AC:

2132

AN:

249750

Hom.:

AF XY:

0.00877

AC XY:

1184

AN XY:

134982

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.0373

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00455

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.0115

GnomAD4 exome

AF:

0.0106

AC:

15522

AN:

1460148

Hom.:

127

Cov.:

AF XY:

0.0107

AC XY:

7736

AN XY:

726144

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00298

Gnomad4 ASJ exome

AF:

0.0385

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00301

Gnomad4 FIN exome

AF:

0.00427

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00766

AC:

1166

AN:

152302

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

515

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00197

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.0386

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00763

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0126

AC:

108

ExAC

AF:

0.00876

AC:

1063

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.0118

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

Cadd

Benign

0.0050

Dann

Benign

0.26

DEOGEN2

Benign

0.027

T;.;.;.;.;.;.;T;T;.;T;T;T;T;T;T;.;T;T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.50

T;.;.;.;.;.;T;.;T;T;.;.;T;.;.;.;T;.;.;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.36

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.82

N;N;N;N;N;N;N;.;.;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.18

Sift4G

Benign

0.34

T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;T;T;T;T;T;T

Polyphen

0.0

.;.;.;.;.;.;.;B;B;.;.;B;.;.;B;B;.;B;B;.;.

Vest4

0.045, 0.069, 0.059, 0.055, 0.060

MVP

0.63

MPC

0.37

ClinPred

0.0013

GERP RS

-2.5

Varity_R

0.028

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over