Genetic Variant ENST00000591891.5:c.-272+21586C>T (chr17-70075206-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000591891.5(KCNJ16):c.-272+21586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,110 control chromosomes in the GnomAD database, including 1,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1895 hom., cov: 32)

Exomes 𝑓: 0.15 ( 1 hom. )

Consequence

KCNJ16
ENST00000591891.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.19

Publications

4 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 17-70075206-C-T is Benign according to our data. Variant chr17-70075206-C-T is described in ClinVar as Benign. ClinVar VariationId is 1289569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000591891.5. 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.-484C>T	upstream_gene	N/A	NP_733937.3	Q9NPI9
KCNJ16	NM_001270422.2		c.-693C>T	upstream_gene	N/A	NP_001257351.1	Q9NPI9
KCNJ16	NM_001291622.3		c.-647C>T	upstream_gene	N/A	NP_001278551.2	Q9NPI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KCNJ16	ENST00000591891.5	TSL:5	c.-272+21586C>T	intron	N/A	ENSP00000465646.1	K7EKJ4
ENSG00000230258	ENST00000435112.5	TSL:3	n.306+52863G>A	intron	N/A
KCNJ16	ENST00000392671.6	TSL:2 MANE Select	c.-484C>T	upstream_gene	N/A	ENSP00000376439.1	Q9NPI9

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23372

AN:

151970

Hom.:

1897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.00967

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0956

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.150

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

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:

0.125

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.154

AC:

23394

AN:

152090

Hom.:

1895

Cov.:

AF XY:

0.151

AC XY:

11234

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.217

AC:

9013

AN:

41446

American (AMR)

AF:

0.136

AC:

2076

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

500

AN:

3470

East Asian (EAS)

AF:

0.00969

AC:

AN:

5160

South Asian (SAS)

AF:

0.109

AC:

525

AN:

4828

European-Finnish (FIN)

AF:

0.0956

AC:

1013

AN:

10592

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9686

AN:

67990

Other (OTH)

AF:

0.182

AC:

385

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1003

2006

3010

4013

5016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.160

Hom.:

379

Bravo

AF:

0.161

Asia WGS

AF:

0.0720

AC:

251

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

-0.39

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

3.2

PromoterAI

-0.14

Neutral

(source)

Splicing

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