rs12940454

Variant names:

• chr17-70110530-G-A
• rs12940454
• NM_170741.4:c.-191+9764G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170741.4(KCNJ16):​c.-191+9764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,348 control chromosomes in the GnomAD database, including 1,217 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 0.11 (1217 hom., cov: 32)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 2 publications found

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: STRONG Submitted by: ClinGen
• hypokalemic tubulopathy and deafness

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000230258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.-191+9764G>A		intron_variant	Intron 2 of 3	ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.-191+9764G>A		intron_variant	Intron 2 of 3	2	NM_170741.4	ENSP00000376439.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17193 AN: 151230 Hom.: 1215 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.121

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17199 AN: 151348 Hom.: 1217 Cov.: 32 AF XY: 0.113 AC XY: 8350 AN XY: 73972

African (AFR) AF: 0.0427 AC: 1764 AN: 41274

American (AMR) AF: 0.107 AC: 1619 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 383 AN: 3462

East Asian (EAS) AF: 0.274 AC: 1411 AN: 5152

South Asian (SAS) AF: 0.119 AC: 569 AN: 4786

European-Finnish (FIN) AF: 0.110 AC: 1160 AN: 10510

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9906 AN: 67716

Other (OTH) AF: 0.120 AC: 252 AN: 2100

Alfa AF: 0.136 Hom.: 918

Bravo AF: 0.108

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12940454; hg19: chr17-68106671;