17-78360015-T-G

Position:

• chr17-78360015-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.-354A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 201,872 control chromosomes in the GnomAD database, including 82,065 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 0.91 (62760 hom., cov: 35)
  • Exomes 𝑓: 0.87 (19305 hom.)
• Consequence: SOCS3 NM_003955.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOCS3	NM_003955.5	c.-354A>C		5_prime_UTR_variant	1/2	ENST00000330871.3
SOCS3	NM_001378933.1	c.-88-832A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOCS3	ENST00000330871.3	c.-354A>C		5_prime_UTR_variant	1/2	1	NM_003955.5	P1
SOCS3	ENST00000587578.1	c.-255A>C		5_prime_UTR_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137693 AN: 151622 Hom.: 62707 Cov.: 35

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.894

GnomAD4 exome AF: 0.875 AC: 43851 AN: 50142 Hom.: 19305 Cov.: 0 AF XY: 0.876 AC XY: 23133 AN XY: 26410

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.866

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.956

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.904

Gnomad4 OTH exome AF: 0.879

GnomAD4 genome AF: 0.908 AC: 137801 AN: 151730 Hom.: 62760 Cov.: 35 AF XY: 0.907 AC XY: 67263 AN XY: 74156

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.946

Gnomad4 FIN AF: 0.896

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.895

Alfa AF: 0.887 Hom.: 2841

Bravo AF: 0.903

Asia WGS AF: 0.842 AC: 2834 AN: 3364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.42

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: rs12953258; hg19: chr17-76356096;