rs371488379
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000218.3(KCNQ1):c.1394-8C>A 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 0.0000774 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.1394-8C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000155840.12 | NP_000209.2 | |||
KCNQ1OT1 | NR_002728.3 | n.38046G>T | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.1394-8C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000218.3 | ENSP00000155840 | P1 | |||
KCNQ1OT1 | ENST00000710656.1 | n.376-20838G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251354Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135888
GnomAD4 exome AF: 0.0000835 AC: 122AN: 1461854Hom.: 0 Cov.: 34 AF XY: 0.0000784 AC XY: 57AN XY: 727224
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 05, 2013 | Variant classified as Uncertain Significance - Favor Benign. The c.1394-8C>A var iant in KCNQ1 has not been reported in individuals with hearing loss or in large population studies. This variant is located in the 3' splice region but not in the invariant ?1/-2 positions. Computational tools do not suggest an impact to s plicing; however, this information is not predictive enough to rule out pathogen icity. In summary, the clinical significance of this variant cannot be determine d with certainty; however, we would lean towards a more likely benign role based on a lack of splicing impact predicted by computational tools. - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at