17-70131049-T-A

Variant names:

• chr17-70131049-T-A
• rs9913355
• NM_170741.4:c.-94+74T>A

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+74T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,375,272 control chromosomes in the GnomAD database, including 2,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (1222 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (979 hom.)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.807
• 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 17-70131049-T-A is Benign according to our data. Variant chr17-70131049-T-A is described in ClinVar as Benign. ClinVar VariationId is 1291190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 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+74T>A		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-222+74T>A		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+74T>A		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+74T>A		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+74T>A		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+74T>A		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10356 AN: 151878 Hom.: 1211 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0517

GnomAD4 exome AF: 0.00740 AC: 9057 AN: 1223278 Hom.: 979 AF XY: 0.00641 AC XY: 3922 AN XY: 611536

African (AFR) AF: 0.253 AC: 7179 AN: 28352

American (AMR) AF: 0.0134 AC: 476 AN: 35504

Ashkenazi Jewish (ASJ) AF: 0.000495 AC: 12 AN: 24240

East Asian (EAS) AF: 0.00 AC: 0 AN: 34996

South Asian (SAS) AF: 0.000448 AC: 34 AN: 75924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33834

Middle Eastern (MID) AF: 0.0141 AC: 77 AN: 5450

European-Non Finnish (NFE) AF: 0.000424 AC: 395 AN: 932398

Other (OTH) AF: 0.0168 AC: 884 AN: 52580

GnomAD4 genome AF: 0.0684 AC: 10400 AN: 151994 Hom.: 1222 Cov.: 31 AF XY: 0.0664 AC XY: 4936 AN XY: 74300

African (AFR) AF: 0.237 AC: 9810 AN: 41346

American (AMR) AF: 0.0266 AC: 406 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 68002

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0556 Hom.: 113

Bravo AF: 0.0798

Asia WGS AF: 0.0160 AC: 58 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	0.26
DANN	Benign	0.46
PhyloP100		-0.81
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: rs9913355; hg19: chr17-68127190;