17-78357829-T-C

Position:

• chr17-78357829-T-C

Variant summary

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

The ENST00000330871.3(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 ENST00000330871.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOCS3	NM_003955.5	c.*589A>G		3_prime_UTR_variant	2/2	ENST00000330871.3	NP_003946.3
SOCS3	NM_001378932.1	c.*589A>G		3_prime_UTR_variant	2/2		NP_001365861.1
SOCS3	NM_001378933.1	c.*589A>G		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.*589A>G		3_prime_UTR_variant	2/2	1	NM_003955.5	ENSP00000330341	P1

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

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.917

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.967

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.778

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

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.923

Gnomad4 OTH AF: 0.903

Alfa AF: 0.911 Hom.: 22272

Bravo AF: 0.913

Asia WGS AF: 0.856 AC: 2978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4969169; hg19: chr17-76353910;