rs9906557

Variant names:

• chr17-70131052-C-T
• rs9906557
• NM_170741.4:c.-94+77C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-70131052-C-T
• chr17-70131052-C-G

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.-94+77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,333,036 control chromosomes in the GnomAD database, including 2,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (1196 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (928 hom.)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-70131052-C-T is Benign according to our data. Variant chr17-70131052-C-T is described in ClinVar as Benign. ClinVar VariationId is 1175594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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+77C>T		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-222+77C>T		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+77C>T		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+77C>T		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+77C>T		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+77C>T		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10251 AN: 151660 Hom.: 1185 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000971

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.00741 AC: 8749 AN: 1181258 Hom.: 928 AF XY: 0.00640 AC XY: 3796 AN XY: 592680

African (AFR) AF: 0.251 AC: 6921 AN: 27598

American (AMR) AF: 0.0133 AC: 471 AN: 35466

Ashkenazi Jewish (ASJ) AF: 0.000501 AC: 12 AN: 23964

East Asian (EAS) AF: 0.00 AC: 0 AN: 34820

South Asian (SAS) AF: 0.000453 AC: 34 AN: 75114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33826

Middle Eastern (MID) AF: 0.0143 AC: 77 AN: 5376

European-Non Finnish (NFE) AF: 0.000428 AC: 383 AN: 893920

Other (OTH) AF: 0.0166 AC: 851 AN: 51174

GnomAD4 genome AF: 0.0678 AC: 10295 AN: 151778 Hom.: 1196 Cov.: 31 AF XY: 0.0659 AC XY: 4884 AN XY: 74166

African (AFR) AF: 0.235 AC: 9707 AN: 41272

American (AMR) AF: 0.0265 AC: 404 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 67970

Other (OTH) AF: 0.0511 AC: 108 AN: 2114

Alfa AF: 0.0889 Hom.: 196

Bravo AF: 0.0792

Asia WGS AF: 0.0160 AC: 57 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	-0.82
CADD	Benign	0.62
DANN	Benign	0.45
PhyloP100		-1.0
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: rs9906557; hg19: chr17-68127193;