Genetic Variant NM_002240.5:c.*7018C>T (chr21-37618141-G-A) – 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.*7018C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,222 control chromosomes in the GnomAD database, including 6,908 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 ( 6903 hom., cov: 33)

Exomes 𝑓: 0.30 ( 5 hom. )

Consequence

KCNJ6
NM_002240.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

Publications

2 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5 link	c.*7018C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000609713.2	NP_002231.1	P48051
KCNJ6-AS1	NR_183540.1 link	n.408-80414G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNJ6	ENST00000609713.2 link	c.*7018C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_002240.5	ENSP00000477437.1	P48051
ENSG00000286717	ENST00000667151.1 link	n.160+24005G>A	intron_variant	Intron 1 of 2
ENSG00000286717	ENST00000838658.1 link	n.234+24005G>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44724

AN:

152034

Hom.:

6893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.508

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.295

GnomAD4 exome

AF:

0.300

AC:

AN:

Hom.:

Cov.:

AF XY:

0.308

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.323

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.580

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.294

AC:

44767

AN:

152152

Hom.:

6903

Cov.:

AF XY:

0.295

AC XY:

21974

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.265

AC:

10996

AN:

41500

American (AMR)

AF:

0.233

AC:

3570

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

1069

AN:

3472

East Asian (EAS)

AF:

0.135

AC:

698

AN:

5172

South Asian (SAS)

AF:

0.338

AC:

1630

AN:

4824

European-Finnish (FIN)

AF:

0.365

AC:

3867

AN:

10582

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21769

AN:

67992

Other (OTH)

AF:

0.291

AC:

615

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1634

3268

4903

6537

8171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

462

924

1386

1848

2310

<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:

0.310

Hom.:

9767

Bravo

AF:

0.284

Asia WGS

AF:

0.197

AC:

691

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.3

(source)

DANN

Benign

0.51

PhyloP100

0.13

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over