rs2269350
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002295.6(RPSA):c.519G>A(p.Leu173=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,607,196 control chromosomes in the GnomAD database, including 77,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.27 ( 6021 hom., cov: 32)
Exomes 𝑓: 0.31 ( 71213 hom. )
Consequence
RPSA
NM_002295.6 synonymous
NM_002295.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.450
Genes affected
RPSA (HGNC:6502): (ribosomal protein SA) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Many of the effects of laminin are mediated through interactions with cell surface receptors. These receptors include members of the integrin family, as well as non-integrin laminin-binding proteins. This gene encodes a high-affinity, non-integrin family, laminin receptor 1. This receptor has been variously called 67 kD laminin receptor, 37 kD laminin receptor precursor (37LRP) and p40 ribosome-associated protein. The amino acid sequence of laminin receptor 1 is highly conserved through evolution, suggesting a key biological function. It has been observed that the level of the laminin receptor transcript is higher in colon carcinoma tissue and lung cancer cell line than their normal counterparts. Also, there is a correlation between the upregulation of this polypeptide in cancer cells and their invasive and metastatic phenotype. Multiple copies of this gene exist, however, most of them are pseudogenes thought to have arisen from retropositional events. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 3-39411669-G-A is Benign according to our data. Variant chr3-39411669-G-A is described in ClinVar as [Benign]. Clinvar id is 403396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.45 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPSA | NM_002295.6 | c.519G>A | p.Leu173= | synonymous_variant | 5/7 | ENST00000301821.11 | |
RPSA | NM_001304288.2 | c.534G>A | p.Leu178= | synonymous_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPSA | ENST00000301821.11 | c.519G>A | p.Leu173= | synonymous_variant | 5/7 | 1 | NM_002295.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.268 AC: 40671AN: 151982Hom.: 6010 Cov.: 32
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GnomAD3 exomes AF: 0.293 AC: 72494AN: 246998Hom.: 11000 AF XY: 0.296 AC XY: 39622AN XY: 133910
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GnomAD4 exome AF: 0.311 AC: 452766AN: 1455096Hom.: 71213 Cov.: 41 AF XY: 0.310 AC XY: 224477AN XY: 724198
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GnomAD4 genome ? AF: 0.268 AC: 40695AN: 152100Hom.: 6021 Cov.: 32 AF XY: 0.267 AC XY: 19885AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Familial isolated congenital asplenia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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