rs4839282

Positions:

• chr1-110271507-T-A
• chr1-110271507-T-C

Variant summary

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

The XM_006710625.5(KCNC4):​c.1820-11027T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,986 control chromosomes in the GnomAD database, including 23,723 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 0.56 (23723 hom., cov: 31)
• Consequence: KCNC4 XM_006710625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC4	XM_006710625.5	c.1820-11027T>A		intron_variant			XP_006710688.1
KCNC4	XM_047419679.1	c.883-11027T>A		intron_variant			XP_047275635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC4	ENST00000412512.2	n.31-11027T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84379 AN: 151868 Hom.: 23707 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.556 AC: 84459 AN: 151986 Hom.: 23723 Cov.: 31 AF XY: 0.559 AC XY: 41516 AN XY: 74270

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.528

Alfa AF: 0.480 Hom.: 1504

Bravo AF: 0.552

Asia WGS AF: 0.531 AC: 1849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4839282; hg19: chr1-110814129;