rs116103203
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000218.3(KCNQ1):c.386+16242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000332 in 1,366,530 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0018 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
KCNQ1
NM_000218.3 intron
NM_000218.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.528
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 11-2461726-G-A is Benign according to our data. Variant chr11-2461726-G-A is described in ClinVar as [Benign]. Clinvar id is 178384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNQ1 | NM_000218.3 | c.386+16242G>A | intron_variant | ENST00000155840.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNQ1 | ENST00000155840.12 | c.386+16242G>A | intron_variant | 1 | NM_000218.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00177 AC: 270AN: 152192Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000455 AC: 113AN: 248130Hom.: 0 AF XY: 0.000372 AC XY: 50AN XY: 134272
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GnomAD4 exome AF: 0.000152 AC: 184AN: 1214220Hom.: 0 Cov.: 31 AF XY: 0.000143 AC XY: 86AN XY: 601616
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GnomAD4 genome ? AF: 0.00177 AC: 270AN: 152310Hom.: 2 Cov.: 33 AF XY: 0.00161 AC XY: 120AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 18, 2017 | 5+12G>A in Intron 01 of KCNQ1: This variant is not expected to have clinical sig nificance because it is not located within the conserved splice consensus sequen ce and has been identified in 0.6% (144/23872) of African chromosomes by the Gen ome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs1161 03203). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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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