rs558061753
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_004260.4(RECQL4):c.2059-8_2059-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000715 in 1,545,812 control chromosomes in the GnomAD database, including 6 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00050 ( 5 hom. )
Consequence
RECQL4
NM_004260.4 splice_region, splice_polypyrimidine_tract, intron
NM_004260.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.06
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 -16 ACMG points.
BP6
?
Variant 8-144513717-TGAG-T is Benign according to our data. Variant chr8-144513717-TGAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 414231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144513717-TGAG-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00268 (402/150218) while in subpopulation AFR AF= 0.00854 (348/40772). AF 95% confidence interval is 0.0078. There are 1 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2059-8_2059-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2059-8_2059-6del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004260.4 | P1 | |||
ENST00000580385.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00269 AC: 404AN: 150098Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000850 AC: 130AN: 152926Hom.: 4 AF XY: 0.000654 AC XY: 53AN XY: 81082
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GnomAD4 exome AF: 0.000504 AC: 703AN: 1395594Hom.: 5 AF XY: 0.000500 AC XY: 344AN XY: 688220
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GnomAD4 genome ? AF: 0.00268 AC: 402AN: 150218Hom.: 1 Cov.: 32 AF XY: 0.00273 AC XY: 200AN XY: 73246
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 18, 2020 | - - |
Baller-Gerold syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Sep 10, 2020 | - - |
Computational scores
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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