11-2583556-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000218.3(KCNQ1):c.1032+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,589,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000218.3 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.1032+11C>T | intron_variant | Intron 7 of 15 | 1 | NM_000218.3 | ENSP00000155840.2 | |||
KCNQ1 | ENST00000335475.6 | c.651+11C>T | intron_variant | Intron 7 of 15 | 1 | ENSP00000334497.5 | ||||
KCNQ1 | ENST00000496887.7 | c.771+11C>T | intron_variant | Intron 8 of 15 | 5 | ENSP00000434560.2 | ||||
KCNQ1 | ENST00000646564.2 | c.588+11C>T | intron_variant | Intron 3 of 10 | ENSP00000495806.2 |
Frequencies
GnomAD3 genomes AF: 0.00134 AC: 204AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000394 AC: 99AN: 251070Hom.: 0 AF XY: 0.000339 AC XY: 46AN XY: 135850
GnomAD4 exome AF: 0.000156 AC: 224AN: 1437080Hom.: 0 Cov.: 27 AF XY: 0.000123 AC XY: 88AN XY: 716580
GnomAD4 genome AF: 0.00134 AC: 204AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.00133 AC XY: 99AN XY: 74480
ClinVar
Submissions by phenotype
not specified Benign:2
1032+11C>T in Intron 07 of KCNQ1: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 0.5% (20/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). -
Variant summary: KCNQ1 c.1032+11C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00039 in 251070 control chromosomes, predominantly at a frequency of 0.0046 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 46-fold of the estimated maximal expected allele frequency for a pathogenic variant in KCNQ1 causing Arrhythmia phenotype (0.0001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1032+11C>T has been reported in the literature in a study evaluating high resolution melting (HRM) analysis for KCNQ1 and KCNH2 genes (Millat_2011). This report does not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
not provided Benign:1
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Long QT syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at