Genetic Variant NM_003955.5:c.-354A>C (chr17-78360015-T-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.-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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

25 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=-0.85).

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 rank	MANE	Protein	UniProt
SOCS3	NM_003955.5 link	c.-354A>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000330871.3	NP_003946.3	O14543Q6FI39
SOCS3	NM_001378933.1 link	c.-88-832A>C		intron_variant	Intron 1 of 1		NP_001365862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS3	ENST00000330871.3 link	c.-354A>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_003955.5	ENSP00000330341.2		O14543

Frequencies

GnomAD3 genomes

AF:

0.908

AC:

137693

AN:

151622

Hom.:

62707

Cov.:

show subpopulations

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.:

AF XY:

0.876

AC XY:

23133

AN XY:

26410

show subpopulations

African (AFR)

AF:

0.927

AC:

871

AN:

940

American (AMR)

AF:

0.847

AC:

878

AN:

1036

Ashkenazi Jewish (ASJ)

AF:

0.866

AC:

1157

AN:

1336

East Asian (EAS)

AF:

0.683

AC:

3785

AN:

5538

South Asian (SAS)

AF:

0.956

AC:

939

AN:

982

European-Finnish (FIN)

AF:

0.879

AC:

5766

AN:

6562

Middle Eastern (MID)

AF:

0.931

AC:

216

AN:

232

European-Non Finnish (NFE)

AF:

0.904

AC:

27987

AN:

30954

Other (OTH)

AF:

0.879

AC:

2252

AN:

2562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

241

482

723

964

1205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.908

AC:

137801

AN:

151730

Hom.:

62760

Cov.:

AF XY:

0.907

AC XY:

67263

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.936

AC:

38807

AN:

41476

American (AMR)

AF:

0.893

AC:

13615

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.893

AC:

3098

AN:

3470

East Asian (EAS)

AF:

0.683

AC:

3500

AN:

5122

South Asian (SAS)

AF:

0.946

AC:

4569

AN:

4832

European-Finnish (FIN)

AF:

0.896

AC:

9331

AN:

10412

Middle Eastern (MID)

AF:

0.938

AC:

272

AN:

290

European-Non Finnish (NFE)

AF:

0.912

AC:

61908

AN:

67868

Other (OTH)

AF:

0.895

AC:

1885

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

648

1296

1944

2592

3240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.887

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

(source)

DANN

Benign

0.42

PhyloP100

-1.8

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over