chr12-93589778-C-T

Variant names:

• chr12-93589778-C-T
• rs7953508
• XM_011538935.2:c.591+14605C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The XM_011538935.2(SOCS2):​c.591+14605C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,106 control chromosomes in the GnomAD database, including 8,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (8312 hom., cov: 33)
• Consequence: SOCS2 XM_011538935.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587

Genes affected

SOCS2 (HGNC:19382): (suppressor of cytokine signaling 2) This gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS family members are cytokine-inducible negative regulators of cytokine receptor signaling via the Janus kinase/signal transducer and activation of transcription pathway (the JAK/STAT pathway). SOCS family proteins interact with major molecules of signaling complexes to block further signal transduction, in part, by proteasomal depletion of receptors or signal-transducing proteins via ubiquitination. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10, interferon (IFN)-gamma and by cytokine receptors such as growth horomone receptor. The protein encoded by this gene interacts with the cytoplasmic domain of insulin-like growth factor-1 receptor (IGF1R) and is thought to be involved in the regulation of IGF1R mediated cell signaling. This gene has pseudogenes on chromosomes 20 and 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS2	XM_011538935.2	c.591+14605C>T		intron_variant	Intron 2 of 2		XP_011537237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48449 AN: 151986 Hom.: 8290 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48521 AN: 152106 Hom.: 8312 Cov.: 33 AF XY: 0.315 AC XY: 23400 AN XY: 74356

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.291

Alfa AF: 0.266 Hom.: 11256

Bravo AF: 0.330

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7953508; hg19: chr12-93983554;