rs587778691
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_003745.2(SOCS1):βc.144_149delβ(p.Ala49_Pro50del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000388 in 1,464,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.00023 ( 0 hom., cov: 33)
Exomes π: 0.00041 ( 0 hom. )
Consequence
SOCS1
NM_003745.2 inframe_deletion
NM_003745.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.07
Genes affected
SOCS1 (HGNC:19383): (suppressor of cytokine signaling 1) This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival. [provided by RefSeq, Jul 2008]
RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00023 (35/151950) while in subpopulation NFE AF= 0.000427 (29/67964). AF 95% confidence interval is 0.000304. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd4 at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOCS1 | NM_003745.2 | c.144_149del | p.Ala49_Pro50del | inframe_deletion | 2/2 | ENST00000332029.4 | |
LOC105371082 | XR_933070.4 | n.178+5561_178+5566del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOCS1 | ENST00000332029.4 | c.144_149del | p.Ala49_Pro50del | inframe_deletion | 2/2 | 1 | NM_003745.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000230 AC: 35AN: 151950Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000214 AC: 15AN: 70188Hom.: 0 AF XY: 0.000147 AC XY: 6AN XY: 40826
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GnomAD4 exome AF: 0.000406 AC: 533AN: 1312470Hom.: 0 AF XY: 0.000362 AC XY: 234AN XY: 646374
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GnomAD4 genome ? AF: 0.000230 AC: 35AN: 151950Hom.: 0 Cov.: 33 AF XY: 0.000283 AC XY: 21AN XY: 74234
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2022 | In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at