chr11-17771838-C-T
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001112741.2(KCNC1):c.744C>T(p.Ile248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 1,614,160 control chromosomes in the GnomAD database, including 1,462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 120 hom., cov: 33)
Exomes 𝑓: 0.041 ( 1342 hom. )
Consequence
KCNC1
NM_001112741.2 synonymous
NM_001112741.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.320
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
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 11-17771838-C-T is Benign according to our data. Variant chr11-17771838-C-T is described in ClinVar as [Benign]. Clinvar id is 475360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.32 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC1 | NM_001112741.2 | c.744C>T | p.Ile248= | synonymous_variant | 2/4 | ENST00000265969.8 | |
KCNC1 | NM_004976.4 | c.744C>T | p.Ile248= | synonymous_variant | 2/2 | ||
KCNC1 | XM_047426916.1 | c.744C>T | p.Ile248= | synonymous_variant | 2/4 | ||
KCNC1 | XR_930866.3 | n.1966C>T | non_coding_transcript_exon_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC1 | ENST00000265969.8 | c.744C>T | p.Ile248= | synonymous_variant | 2/4 | 5 | NM_001112741.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0312 AC: 4746AN: 152208Hom.: 120 Cov.: 33
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GnomAD3 exomes AF: 0.0306 AC: 7698AN: 251482Hom.: 175 AF XY: 0.0290 AC XY: 3941AN XY: 135912
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GnomAD4 exome AF: 0.0410 AC: 59892AN: 1461834Hom.: 1342 Cov.: 32 AF XY: 0.0400 AC XY: 29100AN XY: 727204
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GnomAD4 genome AF: 0.0312 AC: 4751AN: 152326Hom.: 120 Cov.: 33 AF XY: 0.0316 AC XY: 2355AN XY: 74498
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 25, 2016 | This alteration is classified as 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 submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 15, 2019 | This 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 submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 06, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at