rs45510192
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000218.3(KCNQ1):c.*482G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 457,462 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 138 hom., cov: 33)
Exomes 𝑓: 0.0032 ( 24 hom. )
Consequence
KCNQ1
NM_000218.3 3_prime_UTR
NM_000218.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.829
Genes affected
KCNQ1 (HGNC:6294): (potassium voltage-gated channel subfamily Q member 1) This gene encodes a voltage-gated potassium channel required for repolarization phase of the cardiac action potential. This protein can form heteromultimers with two other potassium channel proteins, KCNE1 and KCNE3. Mutations in this gene are associated with hereditary long QT syndrome 1 (also known as Romano-Ward syndrome), Jervell and Lange-Nielsen syndrome, and familial atrial fibrillation. This gene exhibits tissue-specific imprinting, with preferential expression from the maternal allele in some tissues, and biallelic expression in others. This gene is located in a region of chromosome 11 amongst other imprinted genes that are associated with Beckwith-Wiedemann syndrome (BWS), and itself has been shown to be disrupted by chromosomal rearrangements in patients with BWS. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 11-2848485-G-A is Benign according to our data. Variant chr11-2848485-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 304250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| KCNQ1 | NM_000218.3 | c.*482G>A | 3_prime_UTR_variant | 16/16 | ENST00000155840.12 | NP_000209.2 | ||
| KCNQ1-AS1 | NR_130721.1 | n.778-8043C>T | intron_variant, non_coding_transcript_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KCNQ1 | ENST00000155840.12 | c.*482G>A | 3_prime_UTR_variant | 16/16 | 1 | NM_000218.3 | ENSP00000155840 | P1 | ||
| KCNQ1 | ENST00000335475.6 | c.*482G>A | 3_prime_UTR_variant | 16/16 | 1 | ENSP00000334497 | ||||
| KCNQ1-AS1 | ENST00000440887.2 | n.777-8043C>T | intron_variant, non_coding_transcript_variant | 5 | ||||||
| KCNQ1 | ENST00000496887.7 | c.*482G>A | 3_prime_UTR_variant | 16/16 | 5 | ENSP00000434560 |
Frequencies
GnomAD3 genomes 0.0222 AC: 3372AN: 152160Hom.: 139 Cov.: 33
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GnomAD3 exomes AF: 0.00591 AC: 779AN: 131714Hom.: 23 AF XY: 0.00490 AC XY: 351AN XY: 71640
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GnomAD4 exome AF: 0.00324 AC: 989AN: 305182Hom.: 24 Cov.: 0 AF XY: 0.00258 AC XY: 449AN XY: 173712
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GnomAD4 genome 0.0222 AC: 3375AN: 152280Hom.: 138 Cov.: 33 AF XY: 0.0211 AC XY: 1570AN XY: 74460
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Long QT syndrome 1 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Atrial fibrillation, familial, 3 Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Jervell and Lange-Nielsen syndrome 1 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Short QT syndrome type 2 Benign:1
| Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
| Benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2021 | - - |
Congenital long QT syndrome Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at