rs35029361
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_004260.4(RECQL4):c.2463+6C>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 0.000356 in 1,507,762 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
RECQL4
NM_004260.4 splice_donor_region, intron
NM_004260.4 splice_donor_region, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.856
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 -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 8-144513212-G-A is Benign according to our data. Variant chr8-144513212-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 239730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144513212-G-A is described in Lovd as [Benign]. Variant chr8-144513212-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00215 (256/119006) while in subpopulation AFR AF= 0.00784 (244/31142). AF 95% confidence interval is 0.00703. There are 1 homozygotes in gnomad4. There are 135 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2463+6C>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.2463+6C>T | splice_donor_region_variant, intron_variant | 1 | NM_004260.4 | P1 | |||
RECQL4 | ENST00000621189.4 | c.1392+6C>T | splice_donor_region_variant, intron_variant | 1 | |||||
ENST00000580385.1 | n.271+375G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.635-74C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00214 AC: 255AN: 118982Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000718 AC: 86AN: 119836Hom.: 0 AF XY: 0.000526 AC XY: 34AN XY: 64674
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GnomAD4 exome AF: 0.000202 AC: 281AN: 1388756Hom.: 0 Cov.: 47 AF XY: 0.000184 AC XY: 126AN XY: 686406
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GnomAD4 genome ? AF: 0.00215 AC: 256AN: 119006Hom.: 1 Cov.: 32 AF XY: 0.00236 AC XY: 135AN XY: 57178
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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
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 17, 2020 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
RECQL4-related condition Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 09, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 31, 2021 | - - |
Baller-Gerold syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
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