17-70094066-C-T

Variant names:

• chr17-70094066-C-T
• rs11867479
• NM_170741.4:c.-299-6592C>T

Variant summary

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

The NM_170741.4(KCNJ16):​c.-299-6592C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,030 control chromosomes in the GnomAD database, including 6,962 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 0.28 (6962 hom., cov: 32)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 50 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.-299-6592C>T		intron_variant	Intron 1 of 3	ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.-299-6592C>T		intron_variant	Intron 1 of 3	2	NM_170741.4	ENSP00000376439.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42929 AN: 151914 Hom.: 6965 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.282 AC: 42923 AN: 152030 Hom.: 6962 Cov.: 32 AF XY: 0.282 AC XY: 20929 AN XY: 74300

African (AFR) AF: 0.120 AC: 4979 AN: 41486

American (AMR) AF: 0.337 AC: 5144 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3468

East Asian (EAS) AF: 0.536 AC: 2765 AN: 5158

South Asian (SAS) AF: 0.227 AC: 1097 AN: 4822

European-Finnish (FIN) AF: 0.274 AC: 2891 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23928 AN: 67960

Other (OTH) AF: 0.296 AC: 626 AN: 2112

Alfa AF: 0.331 Hom.: 39559

Bravo AF: 0.285

Asia WGS AF: 0.354 AC: 1233 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.68
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: rs11867479; hg19: chr17-68090207;