rs3816997

Variant names:

• chr12-93577010-A-C
• rs3816997
• ENST00000549510.1:c.114+1837A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-93577010-A-C
• chr12-93577010-A-G
• chr12-93577010-A-T

Variant summary

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

The ENST00000549510.1(SOCS2):​c.114+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
• Publications: 11 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=-0.8).
• 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 rank	MANE	Protein	UniProt
SOCS2	XM_017020155.3	c.591+1837A>C		intron_variant	Intron 2 of 2		XP_016875644.1
SOCS2	XM_011538929.2	c.591+1837A>C		intron_variant	Intron 2 of 2		XP_011537231.1
SOCS2	XM_011538935.2	c.591+1837A>C		intron_variant	Intron 2 of 2		XP_011537237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS2	ENST00000549510.1	c.114+1837A>C		intron_variant	Intron 1 of 1	2		ENSP00000474888.1

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

African (AFR) AF: 0.346 AC: 14340 AN: 41466

American (AMR) AF: 0.203 AC: 3109 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.195 AC: 1008 AN: 5164

South Asian (SAS) AF: 0.164 AC: 793 AN: 4830

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10576

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9340 AN: 67990

Other (OTH) AF: 0.232 AC: 490 AN: 2108

Alfa AF: 0.165 Hom.: 1336

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
PhyloP100		-2.4

Splicing

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

Other links and lift over

dbSNP: rs3816997; hg19: chr12-93970786;