rs163150
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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.1685+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,522,216 control chromosomes in the GnomAD database, including 349,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.66 ( 33412 hom., cov: 33)
Exomes 𝑓: 0.68 ( 315674 hom. )
Consequence
KCNQ1
NM_000218.3 intron
NM_000218.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.25
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=-0.96).
BP6
?
Variant 11-2776090-A-G is Benign according to our data. Variant chr11-2776090-A-G is described in ClinVar as [Benign]. Clinvar id is 1264836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2776090-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.1685+36A>G | intron_variant | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.1685+36A>G | intron_variant | 1 | NM_000218.3 | P1 | |||
KCNQ1 | ENST00000335475.6 | c.1304+36A>G | intron_variant | 1 | |||||
KCNQ1 | ENST00000496887.7 | c.1328+36A>G | intron_variant | 5 | |||||
KCNQ1 | ENST00000646564.2 | c.1145+36A>G | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.661 AC: 100422AN: 151994Hom.: 33369 Cov.: 33
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GnomAD3 exomes AF: 0.668 AC: 101051AN: 151238Hom.: 34175 AF XY: 0.676 AC XY: 53955AN XY: 79814
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GnomAD4 exome AF: 0.678 AC: 929514AN: 1370104Hom.: 315674 Cov.: 25 AF XY: 0.680 AC XY: 459523AN XY: 675698
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GnomAD4 genome ? AF: 0.661 AC: 100522AN: 152112Hom.: 33412 Cov.: 33 AF XY: 0.665 AC XY: 49496AN XY: 74388
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ClinVar
Significance: Benign
Submissions summary: Benign:2
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 | Molecular Genetics Laboratory - Cardiogenetics, CHU de Nantes | Aug 01, 2023 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
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