12-93574421-T-C

Variant names:

• chr12-93574421-T-C
• rs768775
• NM_001270471.2:c.140-301T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270471.2(SOCS2):​c.140-301T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 241,792 control chromosomes in the GnomAD database, including 5,714 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 0.19 (3411 hom., cov: 31)
  • Exomes 𝑓: 0.20 (2303 hom.)
• Consequence: SOCS2 NM_001270471.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.970
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270471.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS2	NM_001270471.2	MANE Select	c.140-301T>C		intron	N/A	NP_001257400.1
	SOCS2	NM_001270467.2		c.140-301T>C		intron	N/A	NP_001257396.1
	SOCS2	NM_001270468.2		c.140-301T>C		intron	N/A	NP_001257397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS2	ENST00000551556.2	TSL:1 MANE Select	c.140-301T>C		intron	N/A	ENSP00000449227.1
	SOCS2	ENST00000340600.6	TSL:1	c.140-301T>C		intron	N/A	ENSP00000339428.2
	SOCS2	ENST00000549122.5	TSL:1	c.140-301T>C		intron	N/A	ENSP00000447161.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29137 AN: 151712 Hom.: 3404 Cov.: 31

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.205 AC: 18437 AN: 89962 Hom.: 2303 Cov.: 0 AF XY: 0.203 AC XY: 9347 AN XY: 45980

African (AFR) AF: 0.0903 AC: 273 AN: 3024

American (AMR) AF: 0.266 AC: 1250 AN: 4700

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 471 AN: 3628

East Asian (EAS) AF: 0.455 AC: 2836 AN: 6234

South Asian (SAS) AF: 0.110 AC: 446 AN: 4038

European-Finnish (FIN) AF: 0.289 AC: 864 AN: 2986

Middle Eastern (MID) AF: 0.128 AC: 59 AN: 460

European-Non Finnish (NFE) AF: 0.188 AC: 11104 AN: 58910

Other (OTH) AF: 0.190 AC: 1134 AN: 5982

GnomAD4 genome AF: 0.192 AC: 29159 AN: 151830 Hom.: 3411 Cov.: 31 AF XY: 0.197 AC XY: 14650 AN XY: 74192

African (AFR) AF: 0.0896 AC: 3717 AN: 41466

American (AMR) AF: 0.281 AC: 4292 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5170

South Asian (SAS) AF: 0.140 AC: 675 AN: 4824

European-Finnish (FIN) AF: 0.303 AC: 3151 AN: 10390

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14183 AN: 67938

Other (OTH) AF: 0.177 AC: 372 AN: 2100

Alfa AF: 0.199 Hom.: 435

Bravo AF: 0.191

Asia WGS AF: 0.237 AC: 824 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.66
DANN	Benign	0.60
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs768775; hg19: chr12-93968197;