rs543599445
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000218.3(KCNQ1):c.1033-4C>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 0.0000229 in 1,613,820 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 Likely benign (★★).
Frequency
Consequence
NM_000218.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.1033-4C>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.1033-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000218.3 | P1 | |||
KCNQ1 | ENST00000335475.6 | c.652-4C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
KCNQ1 | ENST00000496887.7 | c.771+1663C>T | intron_variant | 5 | |||||
KCNQ1 | ENST00000646564.2 | c.588+1663C>T | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251374Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135882
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461468Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727070
GnomAD4 genome ? AF: 0.0000459 AC: 7AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74496
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | Nov 15, 2017 | BP4, BP6; This alteration is predicted to be tolerated by multiple functional prediction tools, and was reported as a benign/likely benign alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory). - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 28, 2017 | c.1033-4C>T in intron 7 of KCNQ1: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 3/66520 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs543599445) - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 29, 2019 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 30, 2024 | This 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. - |
Cardiac arrhythmia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 29, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at