rs17718902

Variant names:

• chr11-17763160-G-A
• rs17718902
• NM_001112741.2:c.571-8505G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-17763160-G-A
• chr11-17763160-G-C
• chr11-17763160-G-T

Variant summary

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

The NM_001112741.2(KCNC1):​c.571-8505G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,878 control chromosomes in the GnomAD database, including 23,331 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 0.53 (23331 hom., cov: 31)
• Consequence: KCNC1 NM_001112741.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 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.571-8505G>A		intron	N/A	NP_001106212.1	P48547-2
	KCNC1	NM_004976.4		c.571-8505G>A		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.571-8505G>A		intron	N/A	ENSP00000265969.7	P48547-2
	KCNC1	ENST00000379472.4	TSL:1	c.571-8505G>A		intron	N/A	ENSP00000368785.3	P48547-1
	KCNC1	ENST00000639325.2	TSL:5	c.571-8505G>A		intron	N/A	ENSP00000492663.2	A0A1W2PNZ3

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80378 AN: 151758 Hom.: 23313 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.529 AC: 80409 AN: 151878 Hom.: 23331 Cov.: 31 AF XY: 0.535 AC XY: 39711 AN XY: 74220

African (AFR) AF: 0.282 AC: 11695 AN: 41406

American (AMR) AF: 0.690 AC: 10527 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2153 AN: 3468

East Asian (EAS) AF: 0.881 AC: 4539 AN: 5150

South Asian (SAS) AF: 0.635 AC: 3057 AN: 4814

European-Finnish (FIN) AF: 0.566 AC: 5976 AN: 10562

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40408 AN: 67908

Other (OTH) AF: 0.578 AC: 1220 AN: 2110

Alfa AF: 0.571 Hom.: 9136

Bravo AF: 0.533

Asia WGS AF: 0.740 AC: 2567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		0.33
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: rs17718902; hg19: chr11-17784707;