Variant chr17-21702905-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001194958.2(KCNJ18):c.119G>A(p.Arg40His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,531,558 control chromosomes in the GnomAD database, including 125,577 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12875 hom., cov: 33)

Exomes 𝑓: 0.43 ( 112702 hom. )

Consequence

KCNJ18
NM_001194958.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

KCNJ18 (HGNC:39080): (potassium inwardly rectifying channel subfamily J member 18) This gene encodes a member of the inwardly rectifying potassium channel family. Transcription of this locus is regulated by thyroid hormone, and the encoded protein plays a role in resting membrane potential maintenance. Mutations in this locus have been associated with thyrotoxic hypokalemic periodic paralysis. [provided by RefSeq, Jan 2013]

KCNJ18 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060729682).

BP6

Variant 17-21702905-G-A is Benign according to our data. Variant chr17-21702905-G-A is described in ClinVar as [Benign]. Clinvar id is 3061031.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ18	NM_001194958.2 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	3/3	ENST00000567955.3	NP_001181887.2
KCNJ18	XM_005276919.4 linkuse as main transcript	c.425G>A	p.Arg142His	missense_variant	2/2		XP_005276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ18	ENST00000567955.3 linkuse as main transcript	c.119G>A	p.Arg40His	missense_variant	3/3	1	NM_001194958.2	ENSP00000457807	P1

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59236

AN:

149776

Hom.:

12868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.415

GnomAD4 exome

AF:

0.429

AC:

592790

AN:

1381654

Hom.:

112702

Cov.:

AF XY:

0.434

AC XY:

297985

AN XY:

686120

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.514

Gnomad4 ASJ exome

AF:

0.397

Gnomad4 EAS exome

AF:

0.829

Gnomad4 SAS exome

AF:

0.564

Gnomad4 FIN exome

AF:

0.397

Gnomad4 NFE exome

AF:

0.411

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.395

AC:

59256

AN:

149904

Hom.:

12875

Cov.:

AF XY:

0.398

AC XY:

29178

AN XY:

73222

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.481

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.788

Gnomad4 SAS

AF:

0.601

Gnomad4 FIN

AF:

0.419

Gnomad4 NFE

AF:

0.447

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.407

Hom.:

1057

Bravo

AF:

0.399

ESP6500AA

AF:

0.142

AC:

626

ESP6500EA

AF:

0.307

AC:

2643

ExAC

AF:

0.350

AC:

42506

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KCNJ18-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DEOGEN2

Benign

0.038

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.1

Sift

Benign

0.063

Sift4G

Uncertain

0.039

Vest4

0.18

ClinPred

0.029

GERP RS

5.3

Varity_R

0.13

gMVP

0.55

Splicing

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