rs4969168

Variant names:

• chr17-78357712-A-G
• rs4969168
• NM_003955.5:c.*706T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 57 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 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.*706T>C		3_prime_UTR	Exon 2 of 2	NP_003946.3
	SOCS3	NM_001378932.1		c.*706T>C		3_prime_UTR	Exon 2 of 2	NP_001365861.1	O14543
	SOCS3	NM_001378933.1		c.*706T>C		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.*706T>C		3_prime_UTR	Exon 2 of 2	ENSP00000330341.2	O14543
	SOCS3	ENST00000907726.1		c.*706T>C		3_prime_UTR	Exon 2 of 2	ENSP00000577785.1
	SOCS3	ENST00000912407.1		c.*706T>C		3_prime_UTR	Exon 3 of 3	ENSP00000582466.1

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

African (AFR) AF: 0.333 AC: 2 AN: 6

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.429 AC: 6 AN: 14

South Asian (SAS) AF: 0.708 AC: 17 AN: 24

European-Finnish (FIN) AF: 0.900 AC: 9 AN: 10

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.874 AC: 180 AN: 206

Other (OTH) AF: 0.714 AC: 10 AN: 14

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

African (AFR) AF: 0.398 AC: 16484 AN: 41420

American (AMR) AF: 0.774 AC: 11829 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2844 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2878 AN: 5172

South Asian (SAS) AF: 0.766 AC: 3691 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8903 AN: 10594

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.870 AC: 59135 AN: 67994

Other (OTH) AF: 0.734 AC: 1546 AN: 2106

Alfa AF: 0.823 Hom.: 86729

Bravo AF: 0.690

Asia WGS AF: 0.640 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.59
PhyloP100		-1.4
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: rs4969168; hg19: chr17-76353793;