11-17743283-G-C

Position:

• chr11-17743283-G-C

Variant summary

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

The NM_001112741.2(KCNC1):​c.570+6711G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,082 control chromosomes in the GnomAD database, including 3,980 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 0.21 (3980 hom., cov: 32)
• Consequence: KCNC1 NM_001112741.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.14

Genes affected

KCNC1 (HGNC:6233): (potassium voltage-gated channel subfamily C member 1) This gene encodes a member of a family of integral membrane proteins that mediate the voltage-dependent potassium ion permeability of excitable membranes. Alternative splicing is thought to result in two transcript variants encoding isoforms that differ at their C-termini. These isoforms have had conflicting names in the literature: the longer isoform has been called both "b" and "alpha", while the shorter isoform has been called both "a" and "beta" (PMIDs 1432046, 12091563). [provided by RefSeq, Oct 2014]

KCNC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNC1	NM_001112741.2	c.570+6711G>C		intron_variant		ENST00000265969.8	NP_001106212.1
KCNC1	NM_004976.4	c.570+6711G>C		intron_variant			NP_004967.1
KCNC1	XM_047426916.1	c.570+6711G>C		intron_variant			XP_047282872.1
KCNC1	XR_930866.3	n.1792+6711G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNC1	ENST00000265969.8	c.570+6711G>C		intron_variant		5	NM_001112741.2	ENSP00000265969.7

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32325 AN: 151964 Hom.: 3967 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0192

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.213 AC: 32359 AN: 152082 Hom.: 3980 Cov.: 32 AF XY: 0.209 AC XY: 15525 AN XY: 74358

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.193

Alfa AF: 0.114 Hom.: 195

Bravo AF: 0.213

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.43

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: rs3893215; hg19: chr11-17764830;