rs727503439
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_005633.4(SOS1):c.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000382 in 1,570,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SOS1
NM_005633.4 5_prime_UTR
NM_005633.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 1.54
Genes affected
SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS1 | NM_005633.4 | c.-15C>T | 5_prime_UTR_variant | 1/23 | ENST00000402219.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS1 | ENST00000402219.8 | c.-15C>T | 5_prime_UTR_variant | 1/23 | 1 | NM_005633.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151882Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000141 AC: 2AN: 1418718Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1AN XY: 705466
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151882Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74192
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2013 | The -15C>T variant in SOS1 has not been previously reported in our laboratory or in the literature. The frequency of this variant in large European American and African American populations cannot be determined from the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS) because coverage at this position was insufficient. This variant is located in the 5' untranslated region (5' UTR) and does not affect the coding sequence of the gene. Although we cannot rule ou t a deleterious impact on the regulation of splicing or translation of SOS1, to date no pathogenic variants have been found in this region of the transcript. In summary, additional studies are needed to determine the clinical significance o f the -15C>T variant. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at