rs2280148

Variant names:

• chr17-78358299-T-G
• rs2280148
• NM_003955.5:c.*119A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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]

SOCS3-DT (HGNC:52799): (SOCS3 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SOCS3	NM_003955.5	c.*119A>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000330871.3	NP_003946.3
SOCS3	NM_001378932.1	c.*119A>C		3_prime_UTR_variant	Exon 2 of 2		NP_001365861.1
SOCS3	NM_001378933.1	c.*119A>C		3_prime_UTR_variant	Exon 2 of 2		NP_001365862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS3	ENST00000330871.3	c.*119A>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_003955.5	ENSP00000330341.2
SOCS3-DT	ENST00000794160.1	n.4T>G		non_coding_transcript_exon_variant	Exon 1 of 4
SOCS3-DT	ENST00000794159.1	n.422+89T>G		intron_variant	Intron 2 of 3
SOCS3-DT	ENST00000794161.1	n.-34T>G		upstream_gene_variant

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

African (AFR) AF: 0.0202 AC: 396 AN: 19578

American (AMR) AF: 0.0106 AC: 304 AN: 28582

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 1036 AN: 19030

East Asian (EAS) AF: 0.194 AC: 6539 AN: 33668

South Asian (SAS) AF: 0.101 AC: 6630 AN: 65326

European-Finnish (FIN) AF: 0.00498 AC: 206 AN: 41402

Middle Eastern (MID) AF: 0.0400 AC: 165 AN: 4120

European-Non Finnish (NFE) AF: 0.0170 AC: 9460 AN: 557060

Other (OTH) AF: 0.0299 AC: 1137 AN: 38042

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

African (AFR) AF: 0.0216 AC: 899 AN: 41544

American (AMR) AF: 0.0130 AC: 199 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 218 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1054 AN: 5154

South Asian (SAS) AF: 0.105 AC: 507 AN: 4828

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0182 AC: 1240 AN: 68010

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0209 Hom.: 50

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
PhyloP100		-0.10
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: rs2280148; hg19: chr17-76354380; COSMIC: COSV58270420; COSMIC: COSV58270420;