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rs73424033

chr11-17772330-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001112741.2(KCNC1):c.1236C>T(p.Ser412=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,614,176 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

KCNC1
NM_001112741.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.112
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-17772330-C-T is Benign according to our data. Variant chr11-17772330-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 475347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.112 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00269 (410/152308) while in subpopulation AFR AF= 0.0095 (395/41558). AF 95% confidence interval is 0.00873. There are 1 homozygotes in gnomad4. There are 213 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 406 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KCNC1NM_001112741.2 linkuse as main transcriptc.1236C>T p.Ser412= synonymous_variant 2/4 ENST00000265969.8
KCNC1NM_004976.4 linkuse as main transcriptc.1236C>T p.Ser412= synonymous_variant 2/2
KCNC1XM_047426916.1 linkuse as main transcriptc.1236C>T p.Ser412= synonymous_variant 2/4
KCNC1XR_930866.3 linkuse as main transcriptn.2458C>T non_coding_transcript_exon_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KCNC1ENST00000265969.8 linkuse as main transcriptc.1236C>T p.Ser412= synonymous_variant 2/45 NM_001112741.2 P1P48547-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00267
AC:
406
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00944
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00192
GnomAD3 exomes
AF:
0.000740
AC:
186
AN:
251220
Hom.:
2
AF XY:
0.000582
AC XY:
79
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.00912
Gnomad AMR exome
AF:
0.000694
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.000328
AC:
480
AN:
1461868
Hom.:
4
Cov.:
31
AF XY:
0.000278
AC XY:
202
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00947
Gnomad4 AMR exome
AF:
0.000693
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000737
Gnomad4 OTH exome
AF:
0.000646
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00269
AC:
410
AN:
152308
Hom.:
1
Cov.:
33
AF XY:
0.00286
AC XY:
213
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00950
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00105
Hom.:
0
Bravo
AF:
0.00277
Asia WGS
AF:
0.00289
AC:
11
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023KCNC1: BP4, BP7, BS1 -
Benign, criteria provided, single submitterclinical testingGeneDxOct 19, 2018- -
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsMay 01, 2018- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 06, 2016This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
KCNC1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesSep 30, 2021This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Progressive myoclonic epilepsy type 7 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
13
Dann
Benign
0.85

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73424033; hg19: chr11-17793877; COSMIC: COSV56395770; COSMIC: COSV56395770; API