dbSNP rs1787422: KCNJ6:c.946+9552G>A (chr21-37704659-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.946+9552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0476 in 148,612 control chromosomes in the GnomAD database, including 498 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 0.048 ( 498 hom., cov: 30)

Consequence

KCNJ6
NM_002240.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0720

Publications

3 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:

KCNJ6-AS1 (HGNC:):

KCNJ6-AS1 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5 link	c.946+9552G>A		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1	P48051
KCNJ6-AS1	NR_183540.1 link	n.548-5655C>T		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ6	ENST00000609713.2 link	c.946+9552G>A	intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1	P48051
KCNJ6	ENST00000645093.1 link	c.946+9552G>A	intron_variant	Intron 4 of 4			ENSP00000493772.1	P48051
KCNJ6-AS1	ENST00000711629.1 link	n.141-5655C>T	intron_variant	Intron 1 of 6
KCNJ6-AS1	ENST00000838485.1 link	n.87-5655C>T	intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7046

AN:

148498

Hom.:

497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0229

Gnomad ASJ

AF:

0.000905

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.0158

Gnomad FIN

AF:

0.000382

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.0406

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

GnomAD4 genome

AF:

0.0476

AC:

7071

AN:

148612

Hom.:

498

Cov.:

AF XY:

0.0464

AC XY:

3373

AN XY:

72740

show subpopulations

African (AFR)

AF:

0.154

AC:

6311

AN:

41050

American (AMR)

AF:

0.0229

AC:

345

AN:

15086

Ashkenazi Jewish (ASJ)

AF:

0.000905

AC:

AN:

3314

East Asian (EAS)

AF:

0.000198

AC:

AN:

5044

South Asian (SAS)

AF:

0.0156

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.000382

AC:

AN:

10468

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00379

AC:

249

AN:

65712

Other (OTH)

AF:

0.0403

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

297

593

890

1186

1483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.553

Hom.:

26203

Asia WGS

AF:

0.0240

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.54

PhyloP100

-0.072

Mutation Taster

=17/83

disease causing

(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