17-70131194-CAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr17-70131194-C-CAAA
• rs36047658
• NM_170741.4:c.-94+232_-94+234dupAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_170741.4(KCNJ16):​c.-94+232_-94+234dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 85,776 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0050 (5 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00502 (431/85776) while in subpopulation AFR AF = 0.0137 (401/29284). AF 95% confidence interval is 0.0126. There are 5 homozygotes in GnomAd4. There are 212 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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+232_-94+234dupAAA		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-221-146_-221-144dupAAA		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+232_-94+234dupAAA		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+220insAAA		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+219_-94+220insAAA		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+219_-94+220insAAA		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.00502 AC: 431 AN: 85774 Hom.: 5 Cov.: 21

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00196

Gnomad SAS AF: 0.00115

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000846

Gnomad OTH AF: 0.00174

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

GnomAD4 genome AF: 0.00502 AC: 431 AN: 85776 Hom.: 5 Cov.: 21 AF XY: 0.00518 AC XY: 212 AN XY: 40940

African (AFR) AF: 0.0137 AC: 401 AN: 29284

American (AMR) AF: 0.00190 AC: 15 AN: 7894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1828

East Asian (EAS) AF: 0.00197 AC: 7 AN: 3558

South Asian (SAS) AF: 0.00115 AC: 3 AN: 2600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 134

European-Non Finnish (NFE) AF: 0.0000847 AC: 3 AN: 35438

Other (OTH) AF: 0.00172 AC: 2 AN: 1160

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

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;