chr17-70075206-C-T

Position:

• chr17-70075206-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000591891.5(KCNJ16):​c.-272+21586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,110 control chromosomes in the GnomAD database, including 1,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1895 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1 hom.)
• Consequence: KCNJ16 ENST00000591891.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.19

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 17-70075206-C-T is Benign according to our data. Variant chr17-70075206-C-T is described in ClinVar as [Benign]. Clinvar id is 1289569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.-484C>T		upstream_gene_variant		ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.-484C>T		upstream_gene_variant		2	NM_170741.4	ENSP00000376439.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23372 AN: 151970 Hom.: 1897 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00967

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0956

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.150 AC: 3 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.154 AC: 23394 AN: 152090 Hom.: 1895 Cov.: 32 AF XY: 0.151 AC XY: 11234 AN XY: 74356

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.00969

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0956

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.182

Alfa AF: 0.159 Hom.: 359

Bravo AF: 0.161

Asia WGS AF: 0.0720 AC: 251 AN: 3478

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	Apr 09, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8076244; hg19: chr17-68071347;