dbSNP rs2835831: KCNJ6:c.*10228A>G (chr21-37614931-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.*10228A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,076 control chromosomes in the GnomAD database, including 6,822 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 0.29 ( 6822 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

KCNJ6
NM_002240.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0280

Publications

4 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:

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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 = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002240.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	NM_002240.5	MANE Select	c.*10228A>G		3_prime_UTR	Exon 4 of 4	NP_002231.1	P48051
	KCNJ6-AS1	NR_183540.1		n.408-83624T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.*10228A>G	3_prime_UTR	Exon 4 of 4	ENSP00000477437.1	P48051
ENSG00000286717	ENST00000667151.1		n.160+20795T>C	intron	N/A
ENSG00000286717	ENST00000838658.1		n.234+20795T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44512

AN:

151950

Hom.:

6812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.291

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.293

AC:

44555

AN:

152070

Hom.:

6822

Cov.:

AF XY:

0.294

AC XY:

21855

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.267

AC:

11083

AN:

41448

American (AMR)

AF:

0.232

AC:

3541

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1068

AN:

3466

East Asian (EAS)

AF:

0.138

AC:

717

AN:

5180

South Asian (SAS)

AF:

0.335

AC:

1613

AN:

4816

European-Finnish (FIN)

AF:

0.365

AC:

3860

AN:

10570

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21468

AN:

67988

Other (OTH)

AF:

0.287

AC:

607

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1593

3185

4778

6370

7963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.312

Hom.:

10401

Bravo

AF:

0.283

Asia WGS

AF:

0.197

AC:

688

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

0.028

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over