rs34437789
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004260.4(RECQL4):c.1258+6A>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,611,922 control chromosomes in the GnomAD database, including 814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.022 ( 51 hom., cov: 34)
Exomes 𝑓: 0.030 ( 763 hom. )
Consequence
RECQL4
NM_004260.4 splice_donor_region, intron
NM_004260.4 splice_donor_region, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.371
Genes affected
RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]
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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=-0.76).
BP6
?
Variant 8-144515758-T-A is Benign according to our data. Variant chr8-144515758-T-A is described in ClinVar as [Benign]. Clinvar id is 259257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515758-T-A is described in Lovd as [Benign]. Variant chr8-144515758-T-A is described in Lovd as [Likely_benign].
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.1258+6A>T | splice_donor_region_variant, intron_variant | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.1258+6A>T | splice_donor_region_variant, intron_variant | 1 | NM_004260.4 | P1 | |||
RECQL4 | ENST00000621189.4 | c.187+6A>T | splice_donor_region_variant, intron_variant | 1 | |||||
RECQL4 | ENST00000532846.2 | c.143+6A>T | splice_donor_region_variant, intron_variant | 5 | |||||
RECQL4 | ENST00000688394.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0225 AC: 3420AN: 152136Hom.: 51 Cov.: 34
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GnomAD3 exomes AF: 0.0242 AC: 5958AN: 246064Hom.: 108 AF XY: 0.0249 AC XY: 3343AN XY: 134110
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GnomAD4 exome AF: 0.0296 AC: 43153AN: 1459668Hom.: 763 Cov.: 65 AF XY: 0.0294 AC XY: 21375AN XY: 726006
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GnomAD4 genome ? AF: 0.0224 AC: 3416AN: 152254Hom.: 51 Cov.: 34 AF XY: 0.0204 AC XY: 1520AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2019 | This variant is associated with the following publications: (PMID: 27247962) - |
Rothmund-Thomson syndrome type 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Baller-Gerold syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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