rs3816997

Positions:

• chr12-93577010-A-C

Variant summary

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

The ENST00000549510.1(SOCS2):​c.116+1837A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,102 control chromosomes in the GnomAD database, including 3,925 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 0.21 (3925 hom., cov: 33)
• Consequence: SOCS2 ENST00000549510.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS2	XM_011538929.2	c.591+1837A>C		intron_variant
SOCS2	XM_011538935.2	c.591+1837A>C		intron_variant
SOCS2	XM_011538936.2	c.591+1837A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS2	ENST00000549510.1	c.116+1837A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31450 AN: 151984 Hom.: 3918 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.207 AC: 31471 AN: 152102 Hom.: 3925 Cov.: 33 AF XY: 0.205 AC XY: 15208 AN XY: 74358

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.232

Alfa AF: 0.164 Hom.: 1181

Bravo AF: 0.223

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.19
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3816997; hg19: chr12-93970786;