chr11-17743283-G-C

Variant names:

• chr11-17743283-G-C
• rs3893215
• NM_001112741.2:c.570+6711G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• progressive myoclonic epilepsy type 7

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• progressive myoclonus epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001112741.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC1	NM_001112741.2	MANE Select	c.570+6711G>C		intron	N/A	NP_001106212.1	P48547-2
	KCNC1	NM_004976.4		c.570+6711G>C		intron	N/A	NP_004967.1	P48547-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNC1	ENST00000265969.8	TSL:5 MANE Select	c.570+6711G>C		intron	N/A	ENSP00000265969.7	P48547-2
	KCNC1	ENST00000379472.4	TSL:1	c.570+6711G>C		intron	N/A	ENSP00000368785.3	P48547-1
	KCNC1	ENST00000639325.2	TSL:5	c.570+6711G>C		intron	N/A	ENSP00000492663.2	A0A1W2PNZ3

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

African (AFR) AF: 0.341 AC: 14124 AN: 41444

American (AMR) AF: 0.133 AC: 2036 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3472

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5188

South Asian (SAS) AF: 0.105 AC: 506 AN: 4824

European-Finnish (FIN) AF: 0.199 AC: 2109 AN: 10584

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12057 AN: 67962

Other (OTH) AF: 0.193 AC: 408 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0040
DANN	Benign	0.43
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3893215; hg19: chr11-17764830;