16-11255329-GGGGGCC-GGGGGCCGGGGCC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003745.2(SOCS1):​c.144_149dupGGCCCC​(p.Pro50_Gly51insAlaPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,464,428 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SOCS1
NM_003745.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOCS1NM_003745.2 linkc.144_149dupGGCCCC p.Pro50_Gly51insAlaPro disruptive_inframe_insertion Exon 2 of 2 ENST00000332029.4 NP_003736.1 O15524Q4JHT5
LOC105371082XR_933070.4 linkn.178+5561_178+5566dupGCCGGG intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SOCS1ENST00000332029.4 linkc.144_149dupGGCCCC p.Pro50_Gly51insAlaPro disruptive_inframe_insertion Exon 2 of 2 1 NM_003745.2 ENSP00000329418.2 O15524

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151950
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000855
AC:
6
AN:
70188
Hom.:
0
AF XY:
0.000122
AC XY:
5
AN XY:
40826
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000168
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000280
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000381
AC:
50
AN:
1312478
Hom.:
0
Cov.:
32
AF XY:
0.0000387
AC XY:
25
AN XY:
646376
show subpopulations
Gnomad4 AFR exome
AF:
0.0000382
Gnomad4 AMR exome
AF:
0.000167
Gnomad4 ASJ exome
AF:
0.0000438
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000853
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000354
Gnomad4 OTH exome
AF:
0.0000184
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151950
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74234
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587778691; hg19: chr16-11349186; API