rs2280148

Positions:

• chr17-78358299-T-G

Variant summary

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

The NM_003955.5(SOCS3):​c.*119A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 959,056 control chromosomes in the GnomAD database, including 1,373 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 0.028 (171 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1202 hom.)
• Consequence: SOCS3 NM_003955.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

Genes affected

SOCS3 (HGNC:19391): (suppressor of cytokine signaling 3) This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS3	NM_003955.5	c.*119A>C		3_prime_UTR_variant	2/2	ENST00000330871.3	NP_003946.3
SOCS3	NM_001378932.1	c.*119A>C		3_prime_UTR_variant	2/2		NP_001365861.1
SOCS3	NM_001378933.1	c.*119A>C		3_prime_UTR_variant	2/2		NP_001365862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOCS3	ENST00000330871.3	c.*119A>C		3_prime_UTR_variant	2/2	1	NM_003955.5	ENSP00000330341	P1

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4252 AN: 152130 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0321 AC: 25873 AN: 806808 Hom.: 1202 Cov.: 11 AF XY: 0.0350 AC XY: 14566 AN XY: 416174

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.0544

Gnomad4 EAS exome AF: 0.194

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.00498

Gnomad4 NFE exome AF: 0.0170

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.0279 AC: 4252 AN: 152248 Hom.: 171 Cov.: 32 AF XY: 0.0299 AC XY: 2223 AN XY: 74418

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.0628

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0215 Hom.: 43

Bravo AF: 0.0276

Asia WGS AF: 0.107 AC: 373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.36

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: rs2280148; hg19: chr17-76354380; COSMIC: COSV58270420; COSMIC: COSV58270420;