17-70131194-CAAAAAAAA-CAAAAAAAAA

Variant names:

• chr17-70131194-C-CA
• rs36047658
• NM_170741.4:c.-94+234dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_170741.4(KCNJ16):​c.-94+234dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 85,342 control chromosomes in the GnomAD database, including 1,047 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (1047 hom., cov: 21)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33
• Publications: 0 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: DEFINITIVE Submitted by: ClinGen
• hypokalemic tubulopathy and deafness

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 17-70131194-C-CA is Benign according to our data. Variant chr17-70131194-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1275437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ16	NM_170741.4	MANE Select	c.-94+234dupA		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-221-144dupA		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+234dupA		intron	N/A	NP_001278551.2	Q9NPI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ16	ENST00000392671.6	TSL:2 MANE Select	c.-94+219_-94+220insA		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+219_-94+220insA		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+219_-94+220insA		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.184 AC: 15695 AN: 85340 Hom.: 1044 Cov.: 21

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.233

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.184 AC: 15704 AN: 85342 Hom.: 1047 Cov.: 21 AF XY: 0.187 AC XY: 7619 AN XY: 40748

African (AFR) AF: 0.120 AC: 3499 AN: 29252

American (AMR) AF: 0.256 AC: 2010 AN: 7852

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 353 AN: 1804

East Asian (EAS) AF: 0.341 AC: 1209 AN: 3542

South Asian (SAS) AF: 0.154 AC: 399 AN: 2594

European-Finnish (FIN) AF: 0.234 AC: 794 AN: 3390

Middle Eastern (MID) AF: 0.239 AC: 32 AN: 134

European-Non Finnish (NFE) AF: 0.201 AC: 7047 AN: 35144

Other (OTH) AF: 0.202 AC: 234 AN: 1156

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
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: rs36047658; hg19: chr17-68127335;