16-11255463-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003745.2(SOCS1):c.16C>G(p.Gln6Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,291,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

SOCS1
NM_003745.2 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.28

Publications

2 publications found

Variant links:

Genes affected

SOCS1 (HGNC:19383): (suppressor of cytokine signaling 1) 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 can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival. [provided by RefSeq, Jul 2008]

SOCS1 links:

RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

RMI2 links:

LOC105371082 (HGNC:):

LOC105371082 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07165387).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003745.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS1	NM_003745.2	MANE Select	c.16C>G	p.Gln6Glu	missense	Exon 2 of 2	NP_003736.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SOCS1	ENST00000332029.4	TSL:1 MANE Select	c.16C>G	p.Gln6Glu	missense	Exon 2 of 2	ENSP00000329418.2
RMI2	ENST00000572173.1	TSL:1	c.-516+5685G>C		intron	N/A	ENSP00000461206.1
SOCS1	ENST00000644787.1		c.16C>G	p.Gln6Glu	missense	Exon 1 of 1	ENSP00000496577.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000702

AC:

AN:

1139714

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

544420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23350

American (AMR)

AF:

0.00

AC:

AN:

8770

Ashkenazi Jewish (ASJ)

AF:

0.000332

AC:

AN:

15060

East Asian (EAS)

AF:

0.00

AC:

AN:

27254

South Asian (SAS)

AF:

0.00

AC:

AN:

28982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4524

European-Non Finnish (NFE)

AF:

0.00000209

AC:

AN:

954992

Other (OTH)

AF:

0.0000215

AC:

AN:

46472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000263

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00585934), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.387

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.37

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.78

M_CAP

Benign

0.053

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PhyloP100

1.3

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.20

REVEL

Benign

0.037

Sift

Benign

0.54

Sift4G

Benign

0.51

Polyphen

0.049

Vest4

0.11

MutPred

0.20

Loss of MoRF binding (P = 0.0622)

MVP

0.45

MPC

0.99

ClinPred

0.072

GERP RS

2.2

Varity_R

0.061

gMVP

0.25

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over