Genetic Variant KCNJ15:c.*988C>T (chr21-38301377-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_170736.3(KCNJ15):c.*988C>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 0.466 in 166,932 control chromosomes in the GnomAD database, including 19,816 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 0.46 ( 17927 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1889 hom. )

Consequence

KCNJ15
NM_170736.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

10 publications found

Variant links:

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

KCNJ15 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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ15	NM_170736.3	MANE Select	c.*988C>T	3_prime_UTR	Exon 3 of 3	NP_733932.1	Q99712
KCNJ15	NM_001276435.2		c.*988C>T	3_prime_UTR	Exon 5 of 5	NP_001263364.1	Q99712
KCNJ15	NM_001276436.2		c.*988C>T	3_prime_UTR	Exon 5 of 5	NP_001263365.1	Q99712

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.*988C>T	3_prime_UTR	Exon 3 of 3	ENSP00000381911.2	Q99712
KCNJ15	ENST00000328656.8	TSL:1	c.*988C>T	3_prime_UTR	Exon 4 of 4	ENSP00000331698.3	Q99712
KCNJ15	ENST00000398930.5	TSL:5	c.*988C>T	3_prime_UTR	Exon 4 of 4	ENSP00000381904.1	Q99712

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70275

AN:

151930

Hom.:

17931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.464

GnomAD4 exome

AF:

0.504

AC:

7507

AN:

14884

Hom.:

1889

Cov.:

AF XY:

0.505

AC XY:

3569

AN XY:

7070

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.750

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.504

AC:

7404

AN:

14696

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

195

391

586

782

977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.462

AC:

70286

AN:

152048

Hom.:

17927

Cov.:

AF XY:

0.458

AC XY:

34025

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.256

AC:

10632

AN:

41464

American (AMR)

AF:

0.499

AC:

7636

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1861

AN:

3472

East Asian (EAS)

AF:

0.288

AC:

1490

AN:

5166

South Asian (SAS)

AF:

0.384

AC:

1852

AN:

4818

European-Finnish (FIN)

AF:

0.512

AC:

5402

AN:

10556

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.588

AC:

39985

AN:

67964

Other (OTH)

AF:

0.461

AC:

976

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1838

3676

5513

7351

9189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.542

Hom.:

91249

Bravo

AF:

0.453

Asia WGS

AF:

0.333

AC:

1163

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.65

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over