rs4969168

Positions:

• chr17-78357712-A-G
• chr17-78357712-A-T

Variant summary

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

The NM_003955.5(SOCS3):​c.*706T>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 0.713 in 152,358 control chromosomes in the GnomAD database, including 41,893 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 0.71 (41791 hom., cov: 31)
  • Exomes 𝑓: 0.82 (102 hom.)
• Consequence: SOCS3 NM_003955.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS3	NM_003955.5	c.*706T>C		3_prime_UTR_variant	2/2	ENST00000330871.3
SOCS3	NM_001378932.1	c.*706T>C		3_prime_UTR_variant	2/2
SOCS3	NM_001378933.1	c.*706T>C		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS3	ENST00000330871.3	c.*706T>C		3_prime_UTR_variant	2/2	1	NM_003955.5	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108351 AN: 151956 Hom.: 41790 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.824 AC: 234 AN: 284 Hom.: 102 Cov.: 0 AF XY: 0.866 AC XY: 161 AN XY: 186

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.713 AC: 108371 AN: 152074 Hom.: 41791 Cov.: 31 AF XY: 0.713 AC XY: 53012 AN XY: 74362

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.734

Alfa AF: 0.837 Hom.: 70093

Bravo AF: 0.690

Asia WGS AF: 0.640 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.59

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: rs4969168; hg19: chr17-76353793;