chr11-2571395-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000218.3(KCNQ1):c.675G>A(p.Ser225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,611,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S225S) has been classified as Likely benign.
Frequency
Consequence
NM_000218.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.675G>A | p.Ser225= | synonymous_variant | 4/16 | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.675G>A | p.Ser225= | synonymous_variant | 4/16 | 1 | NM_000218.3 | P1 | |
KCNQ1 | ENST00000335475.6 | c.294G>A | p.Ser98= | synonymous_variant | 4/16 | 1 | |||
KCNQ1 | ENST00000496887.7 | c.414G>A | p.Ser138= | synonymous_variant | 5/16 | 5 | |||
KCNQ1 | ENST00000646564.2 | c.478-12040G>A | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152078Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000101 AC: 25AN: 248210Hom.: 1 AF XY: 0.0000965 AC XY: 13AN XY: 134774
GnomAD4 exome AF: 0.0000562 AC: 82AN: 1459174Hom.: 1 Cov.: 32 AF XY: 0.0000510 AC XY: 37AN XY: 725996
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
Long QT syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 04, 2016 | p.Ser225Ser in exon 04 of KCNQ1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.1% (13/11492) of Latino chromosomes including one homozygote by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs148566141). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2019 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 2019 | 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 | Aug 14, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at