rs2270412
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002945.5(RPA1):c.1551+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,599,184 control chromosomes in the GnomAD database, including 35,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.17 ( 2741 hom., cov: 32)
Exomes 𝑓: 0.21 ( 32474 hom. )
Consequence
RPA1
NM_002945.5 intron
NM_002945.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.988
Genes affected
RPA1 (HGNC:10289): (replication protein A1) This gene encodes the largest subunit of the heterotrimeric Replication Protein A (RPA) complex, which binds to single-stranded DNA (ssDNA), forming a nucleoprotein complex that plays an important role in DNA metabolism, being involved in DNA replication, repair, recombination, telomere maintenance, and co-ordinating the cellular response to DNA damage through activation of the ataxia telangiectasia and Rad3-related protein (ATR) kinase. The nucleoprotein complex protects the single-stranded DNA from nucleases, prevents formation of secondary structures that would interfere with repair, and co-ordinates the recruitment and departure of different genome maintenance factors. This subunit contains four oligonucleotide/oligosaccharide-binding (OB) domains, though the majority of ssDNA binding occurs in two of these domains. The heterotrimeric complex has two different modes of ssDNA binding, a low-affinity and high-affinity mode, determined by which ssDNA binding domains are utilized. The different binding modes differ in the length of DNA bound and in the proteins with which it interacts, thereby playing a role in regulating different genomic maintenance pathways. [provided by RefSeq, Sep 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-1888880-G-A is Benign according to our data. Variant chr17-1888880-G-A is described in ClinVar as [Benign]. Clinvar id is 2688163.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPA1 | NM_002945.5 | c.1551+29G>A | intron_variant | ENST00000254719.10 | |||
RPA1 | NM_001355120.2 | c.1512+29G>A | intron_variant | ||||
RPA1 | NM_001355121.2 | c.1375-2953G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPA1 | ENST00000254719.10 | c.1551+29G>A | intron_variant | 1 | NM_002945.5 | P1 | |||
RPA1 | ENST00000574049.1 | c.643-2953G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.169 AC: 25691AN: 152084Hom.: 2746 Cov.: 32
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GnomAD3 exomes AF: 0.215 AC: 52365AN: 243968Hom.: 5927 AF XY: 0.216 AC XY: 28442AN XY: 131666
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GnomAD4 exome AF: 0.208 AC: 300895AN: 1446982Hom.: 32474 Cov.: 31 AF XY: 0.209 AC XY: 149956AN XY: 717836
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GnomAD4 genome AF: 0.169 AC: 25690AN: 152202Hom.: 2741 Cov.: 32 AF XY: 0.173 AC XY: 12845AN XY: 74408
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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