dbSNP rs2835850: KCNJ6:c.947-15191A>G (chr21-37640675-T-C) – 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.947-15191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,260 control chromosomes in the GnomAD database, including 5,306 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 0.25 ( 5306 hom., cov: 33)

Consequence

KCNJ6
NM_002240.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

5 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 links:

ENSG00000286717 (HGNC:):

ENSG00000286717 links:

KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

KCNJ6-AS1 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5 link	c.947-15191A>G		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1	P48051
KCNJ6-AS1	NR_183540.1 link	n.408-57880T>C		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ6	ENST00000609713.2 link	c.947-15191A>G	intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1	P48051
KCNJ6	ENST00000645093.1 link	c.947-15191A>G	intron_variant	Intron 4 of 4			ENSP00000493772.1	P48051
ENSG00000286717	ENST00000667151.1 link	n.161-5872T>C	intron_variant	Intron 1 of 2
ENSG00000286717	ENST00000838658.1 link	n.235-18519T>C	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37728

AN:

152142

Hom.:

5299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.251

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

GnomAD4 genome

AF:

0.248

AC:

37759

AN:

152260

Hom.:

5306

Cov.:

AF XY:

0.250

AC XY:

18642

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.139

AC:

5756

AN:

41538

American (AMR)

AF:

0.206

AC:

3157

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1021

AN:

3472

East Asian (EAS)

AF:

0.104

AC:

541

AN:

5192

South Asian (SAS)

AF:

0.313

AC:

1511

AN:

4824

European-Finnish (FIN)

AF:

0.360

AC:

3818

AN:

10596

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.307

AC:

20882

AN:

68014

Other (OTH)

AF:

0.252

AC:

534

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1455

2911

4366

5822

7277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.283

Hom.:

8449

Bravo

AF:

0.233

Asia WGS

AF:

0.173

AC:

607

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

(source)

DANN

Benign

0.45

PhyloP100

-1.2

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

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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