rs7217507

Variant names:

• chr17-70108499-A-C
• rs7217507
• NM_170741.4:c.-191+7733A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170741.4(KCNJ16):​c.-191+7733A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,100 control chromosomes in the GnomAD database, including 4,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (4041 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238
• Publications: 1 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

ENSG00000230258 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 17-70108499-A-C is Benign according to our data. Variant chr17-70108499-A-C is described in ClinVar as Benign. ClinVar VariationId is 1228894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 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.-191+7733A>C		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-319+118A>C		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-273+118A>C		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.-191+7733A>C		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-191+118A>C		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-191+118A>C		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25795 AN: 151976 Hom.: 4024 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0614

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 1 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.170 AC: 25861 AN: 152092 Hom.: 4041 Cov.: 32 AF XY: 0.165 AC XY: 12279 AN XY: 74354

African (AFR) AF: 0.417 AC: 17277 AN: 41440

American (AMR) AF: 0.132 AC: 2017 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0787 AC: 273 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5166

South Asian (SAS) AF: 0.0611 AC: 294 AN: 4812

European-Finnish (FIN) AF: 0.0458 AC: 486 AN: 10612

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5116 AN: 68002

Other (OTH) AF: 0.139 AC: 294 AN: 2110

Alfa AF: 0.228 Hom.: 2323

Bravo AF: 0.189

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.63
PhyloP100		-0.24
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: rs7217507; hg19: chr17-68104640;