17-70132118-A-G

Position:

• chr17-70132118-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_170741.4(KCNJ16):​c.31A>G​(p.Ile11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,614,136 control chromosomes in the GnomAD database, including 2,419 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.069 (1256 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (1163 hom.)
• Consequence: KCNJ16 NM_170741.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.23

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004542649).
• BP6: Variant 17-70132118-A-G is Benign according to our data. Variant chr17-70132118-A-G is described in ClinVar as [Benign]. Clinvar id is 1266075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.31A>G	p.Ile11Val	missense_variant	4/4	ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.31A>G	p.Ile11Val	missense_variant	4/4	2	NM_170741.4	ENSP00000376439.1

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10452 AN: 152130 Hom.: 1245 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0183 AC: 4610 AN: 251306 Hom.: 533 AF XY: 0.0134 AC XY: 1823 AN XY: 135822

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000751

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00783

GnomAD4 exome AF: 0.00732 AC: 10699 AN: 1461888 Hom.: 1163 Cov.: 32 AF XY: 0.00633 AC XY: 4604 AN XY: 727246

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000421

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0689 AC: 10496 AN: 152248 Hom.: 1256 Cov.: 32 AF XY: 0.0670 AC XY: 4987 AN XY: 74450

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0266

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0118 Hom.: 431

Bravo AF: 0.0799

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.236 AC: 1042

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.0227 AC: 2752

Asia WGS AF: 0.0170 AC: 61 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.6
DANN	Benign	0.36
DEOGEN2	Benign	0.039	.;T;T;T;T;.;T;.;.;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.40	.;.;.;T;.;T;.;T;T;T
MetaRNN	Benign	0.0045	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.1	.;N;N;N;N;.;N;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.37	.;N;N;.;.;.;N;.;.;.
REVEL	Benign	0.25
Sift	Benign	1.0	.;T;T;.;.;.;T;.;.;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	.;B;B;B;B;.;B;.;.;.
Vest4		0.045, 0.046, 0.025, 0.027
MPC		0.062
ClinPred		0.015	T
GERP RS		6.0
Varity_R		0.022
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs9302912; hg19: chr17-68128259;