rs3782415

Positions:

• chr12-93573979-T-C
• chr12-93573979-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270471.2(SOCS2):​c.140-743T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,000 control chromosomes in the GnomAD database, including 3,536 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 0.20 (3534 hom., cov: 32)
  • Exomes 𝑓: 0.22 (2 hom.)
• Consequence: SOCS2 NM_001270471.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS2	NM_001270471.2	c.140-743T>C		intron_variant		ENST00000551556.2	NP_001257400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS2	ENST00000551556.2	c.140-743T>C		intron_variant		1	NM_001270471.2	ENSP00000449227.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30165 AN: 151824 Hom.: 3527 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.217 AC: 13 AN: 60 Hom.: 2 Cov.: 0 AF XY: 0.239 AC XY: 11 AN XY: 46

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.199 AC: 30196 AN: 151940 Hom.: 3534 Cov.: 32 AF XY: 0.204 AC XY: 15132 AN XY: 74220

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.183

Alfa AF: 0.205 Hom.: 3959

Bravo AF: 0.197

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.4
DANN	Benign	0.56

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

LitVar

Other links and lift over

dbSNP: rs3782415; hg19: chr12-93967755;