rs1212611138
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000218.3(KCNQ1):c.684-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000218.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.684-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.684-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000218.3 | P1 | |||
KCNQ1 | ENST00000335475.6 | c.303-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
KCNQ1 | ENST00000496887.7 | c.423-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
KCNQ1 | ENST00000646564.2 | c.478-11427C>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246118Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133850
GnomAD4 exome AF: 0.00000754 AC: 11AN: 1458952Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5AN XY: 725794
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151972Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74232
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2019 | The c.684-5C>T intronic variant results from a C to T substitution 5 nucleotides upstream from coding exon 5 in the KCNQ1 gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2022 | - - |
Cardiac arrhythmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 11, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at