17-70131194-CAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr17-70131194-C-CAA
• rs36047658
• NM_170741.4:c.-94+233_-94+234dupAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_170741.4(KCNJ16):​c.-94+233_-94+234dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 85,666 control chromosomes in the GnomAD database, including 854 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (854 hom., cov: 21)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 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+233_-94+234dupAA		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-221-145_-221-144dupAA		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+233_-94+234dupAA		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+220insAA		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+219_-94+220insAA		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+219_-94+220insAA		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.106 AC: 9071 AN: 85666 Hom.: 852 Cov.: 21

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0482

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.000882

Gnomad MID AF: 0.0479

Gnomad NFE AF: 0.00963

Gnomad OTH AF: 0.0965

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

GnomAD4 genome AF: 0.106 AC: 9076 AN: 85666 Hom.: 854 Cov.: 21 AF XY: 0.108 AC XY: 4401 AN XY: 40880

African (AFR) AF: 0.254 AC: 7410 AN: 29212

American (AMR) AF: 0.0480 AC: 379 AN: 7890

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 38 AN: 1828

East Asian (EAS) AF: 0.152 AC: 540 AN: 3552

South Asian (SAS) AF: 0.0951 AC: 247 AN: 2596

European-Finnish (FIN) AF: 0.000882 AC: 3 AN: 3400

Middle Eastern (MID) AF: 0.0522 AC: 7 AN: 134

European-Non Finnish (NFE) AF: 0.00963 AC: 341 AN: 35418

Other (OTH) AF: 0.0959 AC: 111 AN: 1158

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36047658; hg19: chr17-68127335;