Variant chr17-21415429-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021012.5(KCNJ12):c.87C>T(p.Asn29=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,311,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 0 hom., cov: 68)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

KCNJ12
NM_021012.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.562

Variant links:

Genes affected

KCNJ12 (HGNC:6258): (potassium inwardly rectifying channel subfamily J member 12) This gene encodes an inwardly rectifying K+ channel which may be blocked by divalent cations. This protein is thought to be one of multiple inwardly rectifying channels which contribute to the cardiac inward rectifier current (IK1). The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

KCNJ12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-21415429-C-T is Benign according to our data. Variant chr17-21415429-C-T is described in ClinVar as [Benign]. Clinvar id is 3060191.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.562 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KCNJ12	NM_021012.5 linkuse as main transcript	c.87C>T	p.Asn29=	synonymous_variant	3/3	ENST00000583088.6
KCNJ12	XM_005256625.6 linkuse as main transcript	c.87C>T	p.Asn29=	synonymous_variant	3/3
KCNJ12	XM_011523831.3 linkuse as main transcript	c.87C>T	p.Asn29=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ12	ENST00000583088.6 linkuse as main transcript	c.87C>T	p.Asn29=	synonymous_variant	3/3	1	NM_021012.5	P1
KCNJ12	ENST00000331718.5 linkuse as main transcript	c.87C>T	p.Asn29=	synonymous_variant	3/3	1		P1

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

24759

AN:

135030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.0915

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.164

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.0480

AC:

8665

AN:

180664

Hom.:

AF XY:

0.0457

AC XY:

4445

AN XY:

97252

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.0462

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0269

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0610

Gnomad OTH exome

AF:

0.0514

GnomAD4 exome

AF:

0.138

AC:

161989

AN:

1175876

Hom.:

Cov.:

202

AF XY:

0.137

AC XY:

80757

AN XY:

588042

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.0945

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.000580

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.183

AC:

24787

AN:

135134

Hom.:

Cov.:

AF XY:

0.180

AC XY:

11934

AN XY:

66312

show subpopulations

Gnomad4 AFR

AF:

0.253

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.178

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.190

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

KCNJ12-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.76

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