chr17-70130650-A-G

Variant names:

• chr17-70130650-A-G
• rs998580
• NM_170741.4:c.-190-229A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_170741.4(KCNJ16):​c.-190-229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,158 control chromosomes in the GnomAD database, including 1,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1518 hom., cov: 31)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.59
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-70130650-A-G is Benign according to our data. Variant chr17-70130650-A-G is described in ClinVar as Benign. ClinVar VariationId is 1293328.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 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.-190-229A>G		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-318-229A>G		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-190-229A>G		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.-190-229A>G		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-190-229A>G		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-190-229A>G		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20532 AN: 152040 Hom.: 1517 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.135 AC: 20540 AN: 152158 Hom.: 1518 Cov.: 31 AF XY: 0.138 AC XY: 10238 AN XY: 74390

African (AFR) AF: 0.102 AC: 4246 AN: 41532

American (AMR) AF: 0.120 AC: 1833 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3462

East Asian (EAS) AF: 0.274 AC: 1416 AN: 5172

South Asian (SAS) AF: 0.142 AC: 685 AN: 4814

European-Finnish (FIN) AF: 0.151 AC: 1605 AN: 10602

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.144 AC: 9759 AN: 67974

Other (OTH) AF: 0.139 AC: 294 AN: 2116

Alfa AF: 0.141 Hom.: 2058

Bravo AF: 0.132

Asia WGS AF: 0.198 AC: 688 AN: 3478

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
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.38
PhyloP100		-1.6
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: rs998580; hg19: chr17-68126791;