rs76929858
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Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_001112741.2(KCNC1):c.72G>A(p.Ser24=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00541 in 1,601,310 control chromosomes in the GnomAD database, including 408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.029 ( 215 hom., cov: 32)
Exomes 𝑓: 0.0030 ( 193 hom. )
Consequence
KCNC1
NM_001112741.2 synonymous
NM_001112741.2 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 3.90
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 -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 11-17736074-G-A is Benign according to our data. Variant chr11-17736074-G-A is described in ClinVar as [Benign]. Clinvar id is 447617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNC1 | NM_001112741.2 | c.72G>A | p.Ser24= | synonymous_variant | 1/4 | ENST00000265969.8 | |
KCNC1 | NM_004976.4 | c.72G>A | p.Ser24= | synonymous_variant | 1/2 | ||
KCNC1 | XM_047426916.1 | c.72G>A | p.Ser24= | synonymous_variant | 1/4 | ||
KCNC1 | XR_930866.3 | n.1294G>A | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNC1 | ENST00000265969.8 | c.72G>A | p.Ser24= | synonymous_variant | 1/4 | 5 | NM_001112741.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0286 AC: 4345AN: 152158Hom.: 216 Cov.: 32
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GnomAD3 exomes AF: 0.00779 AC: 1799AN: 230924Hom.: 82 AF XY: 0.00559 AC XY: 705AN XY: 126008
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GnomAD4 exome AF: 0.00298 AC: 4313AN: 1449034Hom.: 193 Cov.: 32 AF XY: 0.00252 AC XY: 1813AN XY: 719758
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GnomAD4 genome ? AF: 0.0286 AC: 4348AN: 152276Hom.: 215 Cov.: 32 AF XY: 0.0276 AC XY: 2056AN XY: 74462
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 23, 2017 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 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. - |
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 | Jul 31, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at