Variant rs702859 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002240.5(KCNJ6):c.1032C>T(p.Asp344=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,613,624 control chromosomes in the GnomAD database, including 382,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40429 hom., cov: 32)

Exomes 𝑓: 0.68 ( 341960 hom. )

Consequence

KCNJ6
NM_002240.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.344

Variant links:

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

KCNJ6 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 21-37625399-G-A is Benign according to our data. Variant chr21-37625399-G-A is described in ClinVar as [Benign]. Clinvar id is 1170806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.344 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ6	NM_002240.5 linkuse as main transcript	c.1032C>T	p.Asp344=	synonymous_variant	4/4	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1 linkuse as main transcript	n.408-73156G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNJ6	ENST00000609713.2 linkuse as main transcript	c.1032C>T	p.Asp344=	synonymous_variant	4/4	1	NM_002240.5	ENSP00000477437	P1
	ENST00000667151.1 linkuse as main transcript	n.161-21148G>A		intron_variant, non_coding_transcript_variant
KCNJ6	ENST00000645093.1 linkuse as main transcript	c.1032C>T	p.Asp344=	synonymous_variant	5/5			ENSP00000493772	P1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110211

AN:

152004

Hom.:

40392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.775

Gnomad ASJ

AF:

0.698

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.663

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.719

GnomAD3 exomes

AF:

0.711

AC:

177216

AN:

249130

Hom.:

63716

AF XY:

0.702

AC XY:

94910

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.799

Gnomad ASJ exome

AF:

0.695

Gnomad EAS exome

AF:

0.870

Gnomad SAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.633

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.691

GnomAD4 exome

AF:

0.682

AC:

996864

AN:

1461502

Hom.:

341960

Cov.:

AF XY:

0.681

AC XY:

495089

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.806

Gnomad4 AMR exome

AF:

0.798

Gnomad4 ASJ exome

AF:

0.692

Gnomad4 EAS exome

AF:

0.888

Gnomad4 SAS exome

AF:

0.650

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.671

Gnomad4 OTH exome

AF:

0.694

GnomAD4 genome

AF:

0.725

AC:

110299

AN:

152122

Hom.:

40429

Cov.:

AF XY:

0.723

AC XY:

53762

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.801

Gnomad4 AMR

AF:

0.775

Gnomad4 ASJ

AF:

0.698

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.662

Gnomad4 FIN

AF:

0.634

Gnomad4 NFE

AF:

0.680

Gnomad4 OTH

AF:

0.722

Alfa

AF:

0.691

Hom.:

32358

Bravo

AF:

0.738

Asia WGS

AF:

0.810

AC:

2813

AN:

3478

EpiCase

AF:

0.680

EpiControl

AF:

0.670

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Keppen-Lubinsky syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.65

DANN

Benign

0.49

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