17-70131052-C-T

Position:

• chr17-70131052-C-T

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.-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

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 (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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ16	NM_170741.4	c.-94+77C>T		intron_variant		ENST00000392671.6	NP_733937.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ16	ENST00000392671.6	c.-94+77C>T		intron_variant		2	NM_170741.4	ENSP00000376439.1

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

Gnomad4 AFR exome AF: 0.251

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.000501

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000453

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000428

Gnomad4 OTH exome AF: 0.0166

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

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000971

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0815 Hom.: 172

Bravo AF: 0.0792

Asia WGS AF: 0.0160 AC: 57 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	May 12, 2021	- -
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	-0.82
CADD	Benign	0.62
DANN	Benign	0.45

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: rs9906557; hg19: chr17-68127193;