rs778937880

Variant names:

• chr16-11255016-C-A
• NM_003745.2:c.463G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-11255016-C-A
• chr16-11255016-C-G
• chr16-11255016-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003745.2(SOCS1):​c.463G>T​(p.Val155Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V155M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SOCS1 NM_003745.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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]

LOC105371082 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22672716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS1	NM_003745.2	c.463G>T	p.Val155Leu	missense_variant	Exon 2 of 2	ENST00000332029.4	NP_003736.1
LOC105371082	XR_933070.4	n.178+5238C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS1	ENST00000332029.4	c.463G>T	p.Val155Leu	missense_variant	Exon 2 of 2	1	NM_003745.2	ENSP00000329418.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441364 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 716752

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000232

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Uncertain	0.72	D;D
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.54	N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.047
Sift	Benign	0.33	T;.
Sift4G	Benign	0.27	T;.
Polyphen		0.010	B;B
Vest4		0.039
MutPred		0.45		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.41
MPC		0.91
ClinPred		0.31	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-11348873;