Variant rs2070995 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.495A>G(p.Pro165Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,613,810 control chromosomes in the GnomAD database, including 512,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 54328 hom., cov: 32)

Exomes 𝑓: 0.79 ( 458388 hom. )

Consequence

KCNJ6
NM_002240.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.48

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:

KCNJ6-AS1 (HGNC:):

KCNJ6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 21-37714662-T-C is Benign according to our data. Variant chr21-37714662-T-C is described in ClinVar as [Benign]. Clinvar id is 1165658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 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.495A>G	p.Pro165Pro	synonymous_variant	3/4	ENST00000609713.2	NP_002231.1	P48051
KCNJ6-AS1	NR_183540.1 linkuse as main transcript	n.1104T>C		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2 linkuse as main transcript	c.495A>G	p.Pro165Pro	synonymous_variant	3/4	1	NM_002240.5	ENSP00000477437.1		P48051
KCNJ6	ENST00000645093.1 linkuse as main transcript	c.495A>G	p.Pro165Pro	synonymous_variant	4/5			ENSP00000493772.1		P48051

Frequencies

GnomAD3 genomes

AF:

0.841

AC:

127862

AN:

152102

Hom.:

54271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.817

Gnomad ASJ

AF:

0.825

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.841

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.828

Gnomad NFE

AF:

0.791

Gnomad OTH

AF:

0.819

GnomAD3 exomes

AF:

0.803

AC:

200271

AN:

249408

Hom.:

81042

AF XY:

0.801

AC XY:

108415

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.965

Gnomad AMR exome

AF:

0.804

Gnomad ASJ exome

AF:

0.824

Gnomad EAS exome

AF:

0.616

Gnomad SAS exome

AF:

0.829

Gnomad FIN exome

AF:

0.853

Gnomad NFE exome

AF:

0.792

Gnomad OTH exome

AF:

0.796

GnomAD4 exome

AF:

0.790

AC:

1155105

AN:

1461590

Hom.:

458388

Cov.:

AF XY:

0.791

AC XY:

574862

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.969

Gnomad4 AMR exome

AF:

0.806

Gnomad4 ASJ exome

AF:

0.823

Gnomad4 EAS exome

AF:

0.627

Gnomad4 SAS exome

AF:

0.829

Gnomad4 FIN exome

AF:

0.853

Gnomad4 NFE exome

AF:

0.783

Gnomad4 OTH exome

AF:

0.791

GnomAD4 genome

AF:

0.841

AC:

127980

AN:

152220

Hom.:

54328

Cov.:

AF XY:

0.843

AC XY:

62739

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.959

Gnomad4 AMR

AF:

0.817

Gnomad4 ASJ

AF:

0.825

Gnomad4 EAS

AF:

0.620

Gnomad4 SAS

AF:

0.842

Gnomad4 FIN

AF:

0.854

Gnomad4 NFE

AF:

0.791

Gnomad4 OTH

AF:

0.816

Alfa

AF:

0.806

Hom.:

48313

Bravo

AF:

0.837

Asia WGS

AF:

0.762

AC:

2650

AN:

3478

EpiCase

AF:

0.790

EpiControl

AF:

0.790

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	Apr 06, 2021	This variant is associated with the following publications: (PMID: 19760098, 19756153, 20220551) -
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

-0.95

CADD

Benign

0.16

DANN

Benign

0.57

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