17-70130715-A-G

Position:

• chr17-70130715-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_170741.4(KCNJ16):​c.-190-164A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 152,332 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (7 hom., cov: 31)
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.624

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-70130715-A-G is Benign according to our data. Variant chr17-70130715-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1706680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0106 (1618/152332) while in subpopulation NFE AF= 0.0159 (1080/68022). AF 95% confidence interval is 0.0151. There are 7 homozygotes in gnomad4. There are 768 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ16	NM_170741.4	c.-190-164A>G		intron_variant		ENST00000392671.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ16	ENST00000392671.6	c.-190-164A>G		intron_variant		2	NM_170741.4	P1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1617 AN: 152214 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0106 AC: 1618 AN: 152332 Hom.: 7 Cov.: 31 AF XY: 0.0103 AC XY: 768 AN XY: 74492

Gnomad4 AFR AF: 0.00325

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00890

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0114 Hom.: 2

Bravo AF: 0.0121

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 25, 2020

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.48
DANN	Benign	0.36

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: rs150524296; hg19: chr17-68126856;