17-70108499-A-C

Position:

• chr17-70108499-A-C

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.-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

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]

ENSG00000230258 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.-191+7733A>C		intron_variant		ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.-191+7733A>C		intron_variant		2	NM_170741.4	ENSP00000376439.1

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

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.500

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

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0611

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0752

Gnomad4 OTH AF: 0.139

Alfa AF: 0.164 Hom.: 547

Bravo AF: 0.189

Asia WGS AF: 0.0500 AC: 174 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	clinical testing	GeneDx	Apr 09, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.63

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: rs7217507; hg19: chr17-68104640;