17-70112276-T-C

Variant names:

• chr17-70112276-T-C
• rs12936361
• NM_170741.4:c.-191+11510T>C

Variant summary

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

The ENST00000392671.6(KCNJ16):​c.-191+11510T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,010 control chromosomes in the GnomAD database, including 2,930 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 0.19 (2930 hom., cov: 32)
• Consequence: KCNJ16 ENST00000392671.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 4 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392671.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ16	NM_170741.4	MANE Select	c.-191+11510T>C		intron	N/A	NP_733937.3
	KCNJ16	NM_001270422.2		c.-319+3895T>C		intron	N/A	NP_001257351.1
	KCNJ16	NM_001291622.3		c.-191+1834T>C		intron	N/A	NP_001278551.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ16	ENST00000392671.6	TSL:2 MANE Select	c.-191+11510T>C		intron	N/A	ENSP00000376439.1
	KCNJ16	ENST00000283936.5	TSL:1	c.-191+3895T>C		intron	N/A	ENSP00000283936.1
	KCNJ16	ENST00000392670.5	TSL:1	c.-191+3895T>C		intron	N/A	ENSP00000376438.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29101 AN: 151898 Hom.: 2923 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.192 AC: 29125 AN: 152010 Hom.: 2930 Cov.: 32 AF XY: 0.193 AC XY: 14361 AN XY: 74312

African (AFR) AF: 0.230 AC: 9542 AN: 41430

American (AMR) AF: 0.159 AC: 2420 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 565 AN: 3468

East Asian (EAS) AF: 0.317 AC: 1637 AN: 5168

South Asian (SAS) AF: 0.166 AC: 799 AN: 4804

European-Finnish (FIN) AF: 0.164 AC: 1740 AN: 10584

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11826 AN: 67988

Other (OTH) AF: 0.195 AC: 411 AN: 2110

Alfa AF: 0.176 Hom.: 5215

Bravo AF: 0.193

Asia WGS AF: 0.224 AC: 779 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	4.1
DANN	Benign	0.71
PhyloP100		-0.86
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: rs12936361; hg19: chr17-68108417;