Genetic Variant SOCS3:c.*706T>C (chr17-78357712-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.44

Publications

57 publications found

Variant links:

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 links:

SOCS3-DT (HGNC:52799): (SOCS3 divergent transcript)

SOCS3-DT links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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

Gene	Transcript	Tags	HGVSc	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.:

show subpopulations

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.:

AF XY:

0.866

AC XY:

161

AN XY:

186

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.429

AC:

AN:

South Asian (SAS)

AF:

0.708

AC:

AN:

European-Finnish (FIN)

AF:

0.900

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.874

AC:

180

AN:

206

Other (OTH)

AF:

0.714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.713

AC:

108371

AN:

152074

Hom.:

41791

Cov.:

AF XY:

0.713

AC XY:

53012

AN XY:

74362

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1281

2562

3842

5123

6404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.59

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over