rs6682717

Variant names:

• chr1-110273001-G-C
• rs6682717
• ENST00000412512.2:n.31-9533G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000412512.2(KCNC4):​n.31-9533G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,048 control chromosomes in the GnomAD database, including 23,093 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23093 hom., cov: 32)
• Consequence: KCNC4 ENST00000412512.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 2 publications found

Genes affected

KCNC4 (HGNC:6236): (potassium voltage-gated channel subfamily C member 4) The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. It generates atypical voltage-dependent transient current that may be important for neuronal excitability. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC4	XM_006710625.5	c.1820-9533G>C		intron_variant	Intron 3 of 3		XP_006710688.1
KCNC4	XM_047419679.1	c.883-9533G>C		intron_variant	Intron 2 of 2		XP_047275635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNC4	ENST00000412512.2	n.31-9533G>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83124 AN: 151930 Hom.: 23078 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.547 AC: 83203 AN: 152048 Hom.: 23093 Cov.: 32 AF XY: 0.551 AC XY: 40959 AN XY: 74340

African (AFR) AF: 0.479 AC: 19852 AN: 41442

American (AMR) AF: 0.620 AC: 9471 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1781 AN: 3466

East Asian (EAS) AF: 0.497 AC: 2572 AN: 5174

South Asian (SAS) AF: 0.576 AC: 2777 AN: 4820

European-Finnish (FIN) AF: 0.610 AC: 6444 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38609 AN: 67984

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.570 Hom.: 3075

Bravo AF: 0.542

Asia WGS AF: 0.527 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	15
DANN	Benign	0.56
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs6682717; hg19: chr1-110815623;