Genetic Variant KCNJ16:c.-191+7733A>C (chr17-70108499-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_170741.4(KCNJ16):c.-191+7733A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,100 control chromosomes in the GnomAD database, including 4,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4041 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

KCNJ16
NM_170741.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.238

Publications

1 publications found

Variant links:

Genes affected

KCNJ16 (HGNC:6262): (potassium inwardly rectifying channel subfamily J member 16) 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, which tends to allow potassium to flow into rather than out of a cell, can form heterodimers with two other inward-rectifier type potassium channels. It may function in fluid and pH balance regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

KCNJ16 Gene-Disease associations (from GenCC):

hypokalemic alkalosis, familial, with specific renal tubulopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hypokalemic tubulopathy and deafness
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

KCNJ16 links:

ENSG00000230258 (HGNC:):

ENSG00000230258 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 17-70108499-A-C is Benign according to our data. Variant chr17-70108499-A-C is described in ClinVar as Benign. ClinVar VariationId is 1228894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170741.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ16	NM_170741.4	MANE Select	c.-191+7733A>C	intron	N/A	NP_733937.3	Q9NPI9
KCNJ16	NM_001270422.2		c.-319+118A>C	intron	N/A	NP_001257351.1	Q9NPI9
KCNJ16	NM_001291622.3		c.-273+118A>C	intron	N/A	NP_001278551.2	Q9NPI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ16	ENST00000392671.6	TSL:2 MANE Select	c.-191+7733A>C	intron	N/A	ENSP00000376439.1	Q9NPI9
KCNJ16	ENST00000283936.5	TSL:1	c.-191+118A>C	intron	N/A	ENSP00000283936.1	Q9NPI9
KCNJ16	ENST00000392670.5	TSL:1	c.-191+118A>C	intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25795

AN:

151976

Hom.:

4024

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0787

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.0458

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0752

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

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:

0.170

AC:

25861

AN:

152092

Hom.:

4041

Cov.:

AF XY:

0.165

AC XY:

12279

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.417

AC:

17277

AN:

41440

American (AMR)

AF:

0.132

AC:

2017

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0787

AC:

273

AN:

3470

East Asian (EAS)

AF:

0.000774

AC:

AN:

5166

South Asian (SAS)

AF:

0.0611

AC:

294

AN:

4812

European-Finnish (FIN)

AF:

0.0458

AC:

486

AN:

10612

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0752

AC:

5116

AN:

68002

Other (OTH)

AF:

0.139

AC:

294

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

883

1766

2649

3532

4415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.228

Hom.:

2323

Bravo

AF:

0.189

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

2.0

(source)

DANN

Benign

0.63

PhyloP100

-0.24

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over