rs1053090518
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004260.4(RECQL4):c.85-3C>G 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 0.0000027 in 1,483,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004260.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.85-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000621189.4 | c.-990C>G | 5_prime_UTR_variant | 1/20 | 1 | ||||
RECQL4 | ENST00000617875.6 | c.85-3C>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004260.4 | P1 | |||
RECQL4 | ENST00000534538.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151974Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000225 AC: 3AN: 1331858Hom.: 0 Cov.: 32 AF XY: 0.00000305 AC XY: 2AN XY: 656800
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151974Hom.: 0 Cov.: 34 AF XY: 0.0000135 AC XY: 1AN XY: 74254
ClinVar
Submissions by phenotype
Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 08, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 406951). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 1 of the RECQL4 gene. It does not directly change the encoded amino acid sequence of the RECQL4 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at