Variant chr17-70132118-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170741.4(KCNJ16):c.31A>G(p.Ile11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,614,136 control chromosomes in the GnomAD database, including 2,419 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.069 ( 1256 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 1163 hom. )

Consequence

KCNJ16
NM_170741.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.23

Variant links:

Genes affected

KCNJ16 (HGNC:6262): (potassium inwardly rectifying channel subfamily J member 16) 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, which tends to allow potassium to flow into rather than out of a cell, can form heterodimers with two other inward-rectifier type potassium channels. It may function in fluid and pH balance regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

KCNJ16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004542649).

BP6

Variant 17-70132118-A-G is Benign according to our data. Variant chr17-70132118-A-G is described in ClinVar as [Benign]. Clinvar id is 1266075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ16	NM_170741.4 link	c.31A>G	p.Ile11Val	missense_variant	4/4	ENST00000392671.6	NP_733937.3	Q9NPI9K7EJR9A8K434

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6 link	c.31A>G	p.Ile11Val	missense_variant	4/4	2	NM_170741.4	ENSP00000376439.1		Q9NPI9

Frequencies

GnomAD3 genomes

AF:

0.0687

AC:

10452

AN:

152130

Hom.:

1245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.0521

GnomAD3 exomes

AF:

0.0183

AC:

4610

AN:

251306

Hom.:

533

AF XY:

0.0134

AC XY:

1823

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000687

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00732

AC:

10699

AN:

1461888

Hom.:

1163

Cov.:

AF XY:

0.00633

AC XY:

4604

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.000574

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000800

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000421

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

AF:

0.0689

AC:

10496

AN:

152248

Hom.:

1256

Cov.:

AF XY:

0.0670

AC XY:

4987

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.0266

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.0515

Alfa

AF:

0.0118

Hom.:

431

Bravo

AF:

0.0799

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.236

AC:

1042

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0227

AC:

2752

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

6.6

DANN

Benign

0.36

DEOGEN2

Benign

0.039

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

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.40

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

MetaRNN

Benign

0.0045

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

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

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.37

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

REVEL

Benign

0.25

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.045, 0.046, 0.025, 0.027

MPC

0.062

ClinPred

0.015

GERP RS

6.0

Varity_R

0.022

gMVP

0.29

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