Genetic Variant KCNJ6:c.25+24905G>A (chr21-37815753-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002240.5(KCNJ6):c.25+24905G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,232 control chromosomes in the GnomAD database, including 874 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.099 ( 874 hom., cov: 32)

Consequence

KCNJ6
NM_002240.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.906

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

Keppen-Lubinsky syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

KCNJ6 links:

ENSG00000292435 (HGNC:):

ENSG00000292435 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5 link	c.25+24905G>A		intron_variant	Intron 2 of 3	ENST00000609713.2	NP_002231.1	P48051

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ6	ENST00000609713.2 link	c.25+24905G>A	intron_variant	Intron 2 of 3	1	NM_002240.5	ENSP00000477437.1	P48051
KCNJ6	ENST00000645093.1 link	c.25+24905G>A	intron_variant	Intron 3 of 4			ENSP00000493772.1	P48051
ENSG00000292435	ENST00000744133.1 link	n.181-24675C>T	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

15006

AN:

152114

Hom.:

872

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0631

Gnomad ASJ

AF:

0.0988

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0269

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0921

Gnomad OTH

AF:

0.0969

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0988

AC:

15040

AN:

152232

Hom.:

874

Cov.:

AF XY:

0.0974

AC XY:

7247

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.144

AC:

5960

AN:

41524

American (AMR)

AF:

0.0630

AC:

964

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0988

AC:

343

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5180

South Asian (SAS)

AF:

0.0273

AC:

132

AN:

4828

European-Finnish (FIN)

AF:

0.105

AC:

1113

AN:

10592

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0921

AC:

6266

AN:

68012

Other (OTH)

AF:

0.0959

AC:

203

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

696

1391

2087

2782

3478

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0964

Hom.:

129

Bravo

AF:

0.0993

Asia WGS

AF:

0.0330

AC:

117

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.38

(source)

DANN

Benign

0.70

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over