rs4969169

Variant names:

• chr17-78357829-T-C
• rs4969169
• NM_003955.5:c.*589A>G

Variant summary

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

The NM_003955.5(SOCS3):​c.*589A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,564 control chromosomes in the GnomAD database, including 64,266 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 0.92 (64110 hom., cov: 31)
  • Exomes 𝑓: 0.92 (156 hom.)
• Consequence: SOCS3 NM_003955.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 19 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003955.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS3	NM_003955.5	MANE Select	c.*589A>G		3_prime_UTR	Exon 2 of 2	NP_003946.3
	SOCS3	NM_001378932.1		c.*589A>G		3_prime_UTR	Exon 2 of 2	NP_001365861.1	O14543
	SOCS3	NM_001378933.1		c.*589A>G		3_prime_UTR	Exon 2 of 2	NP_001365862.1	O14543

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS3	ENST00000330871.3	TSL:1 MANE Select	c.*589A>G		3_prime_UTR	Exon 2 of 2	ENSP00000330341.2	O14543
	SOCS3	ENST00000907726.1		c.*589A>G		3_prime_UTR	Exon 2 of 2	ENSP00000577785.1
	SOCS3	ENST00000912407.1		c.*589A>G		3_prime_UTR	Exon 3 of 3	ENSP00000582466.1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139354 AN: 152078 Hom.: 64053 Cov.: 31

Gnomad AFR AF: 0.942

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.902

GnomAD4 exome AF: 0.921 AC: 337 AN: 366 Hom.: 156 Cov.: 0 AF XY: 0.944 AC XY: 234 AN XY: 248

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.917 AC: 11 AN: 12

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.333 AC: 2 AN: 6

South Asian (SAS) AF: 0.967 AC: 87 AN: 90

European-Finnish (FIN) AF: 1.00 AC: 12 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.925 AC: 209 AN: 226

Other (OTH) AF: 0.778 AC: 14 AN: 18

GnomAD4 genome AF: 0.916 AC: 139471 AN: 152198 Hom.: 64110 Cov.: 31 AF XY: 0.915 AC XY: 68048 AN XY: 74396

African (AFR) AF: 0.942 AC: 39124 AN: 41534

American (AMR) AF: 0.904 AC: 13819 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3140 AN: 3472

East Asian (EAS) AF: 0.684 AC: 3511 AN: 5136

South Asian (SAS) AF: 0.944 AC: 4548 AN: 4816

European-Finnish (FIN) AF: 0.898 AC: 9520 AN: 10600

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62777 AN: 68028

Other (OTH) AF: 0.903 AC: 1907 AN: 2112

Alfa AF: 0.912 Hom.: 58728

Bravo AF: 0.913

Asia WGS AF: 0.856 AC: 2978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.49
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs4969169; hg19: chr17-76353910;