1-110227601-G-T

Position:

• chr1-110227601-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001039574.3(KCNC4):​c.1819+1423G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,122 control chromosomes in the GnomAD database, including 2,882 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 0.19 (2882 hom., cov: 33)
• Consequence: KCNC4 NM_001039574.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

KCNC4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC4	NM_001039574.3	c.1819+1423G>T		intron_variant		ENST00000438661.3	NP_001034663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC4	ENST00000438661.3	c.1819+1423G>T		intron_variant		1	NM_001039574.3	ENSP00000393655.2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28719 AN: 152004 Hom.: 2880 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.189 AC: 28749 AN: 152122 Hom.: 2882 Cov.: 33 AF XY: 0.189 AC XY: 14037 AN XY: 74362

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.162

Alfa AF: 0.180 Hom.: 5601

Bravo AF: 0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.54

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: rs958798; hg19: chr1-110770223; COSMIC: COSV63925343; COSMIC: COSV63925343;