chr11-2587562-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000218.3(KCNQ1):c.1129-8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,440 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, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.1129-8G>T | splice_region_variant, intron_variant | 1 | NM_000218.3 | ENSP00000155840.2 | ||||
KCNQ1 | ENST00000335475.6 | c.748-8G>T | splice_region_variant, intron_variant | 1 | ENSP00000334497.5 | |||||
KCNQ1 | ENST00000496887.7 | c.772-8G>T | splice_region_variant, intron_variant | 5 | ENSP00000434560.2 | |||||
KCNQ1 | ENST00000646564.2 | c.589-8G>T | splice_region_variant, intron_variant | ENSP00000495806.2 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152140Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250756Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135622
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461300Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726982
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152140Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74320
ClinVar
Submissions by phenotype
Cardiac arrhythmia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 20, 2023 | This variant causes a G to T nucleotide substitution at the -8 position of intron 8 of the KCNQ1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with KCNQ1-related disorders in the literature. This variant has been identified in 3/282120 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at