chr16-11255339-G-GCCGGGA

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_003745.2(SOCS1):c.134_139dupTCCCGG(p.Val45_Pro46dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,428,798 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 1 hom. )

Consequence

SOCS1
NM_003745.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.350

Publications

3 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: Benign. The variant received -10 ACMG points.

BP6

Variant 16-11255339-G-GCCGGGA is Benign according to our data. Variant chr16-11255339-G-GCCGGGA is described in CliVar as Benign. Clinvar id is 135271.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-11255339-G-GCCGGGA is described in CliVar as Benign. Clinvar id is 135271.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-11255339-G-GCCGGGA is described in CliVar as Benign. Clinvar id is 135271.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-11255339-G-GCCGGGA is described in CliVar as Benign. Clinvar id is 135271.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-11255339-G-GCCGGGA is described in CliVar as Benign. Clinvar id is 135271.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-11255339-G-GCCGGGA is described in CliVar as Benign. Clinvar id is 135271.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000835 (127/152060) while in subpopulation AMR AF = 0.00124 (19/15288). AF 95% confidence interval is 0.000889. There are 0 homozygotes in GnomAd4. There are 63 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 127 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOCS1	NM_003745.2 link	c.134_139dupTCCCGG	p.Val45_Pro46dup	conservative_inframe_insertion	Exon 2 of 2	ENST00000332029.4	NP_003736.1	O15524Q4JHT5
LOC105371082	XR_933070.4 link	n.178+5565_178+5570dupGGACCG		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOCS1	ENST00000332029.4 link	c.134_139dupTCCCGG	p.Val45_Pro46dup	conservative_inframe_insertion	Exon 2 of 2	1	NM_003745.2	ENSP00000329418.2		O15524

Frequencies

GnomAD3 genomes

AF:

0.000836

AC:

127

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000291

AC:

AN:

48048

AF XY:

0.000244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000302

Gnomad ASJ exome

AF:

0.000232

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000526

Gnomad OTH exome

AF:

0.000713

GnomAD4 exome

AF:

0.000946

AC:

1208

AN:

1276738

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

607

AN XY:

627500

show subpopulations

African (AFR)

AF:

0.000360

AC:

AN:

24976

American (AMR)

AF:

0.000597

AC:

AN:

16760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20868

East Asian (EAS)

AF:

0.0000357

AC:

AN:

28014

South Asian (SAS)

AF:

0.0000629

AC:

AN:

63598

European-Finnish (FIN)

AF:

0.000137

AC:

AN:

36408

Middle Eastern (MID)

AF:

0.00410

AC:

AN:

4882

European-Non Finnish (NFE)

AF:

0.00108

AC:

1114

AN:

1028568

Other (OTH)

AF:

0.000854

AC:

AN:

52664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<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:

0.000835

AC:

127

AN:

152060

Hom.:

Cov.:

AF XY:

0.000847

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41518

American (AMR)

AF:

0.00124

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000285

AC:

AN:

10542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

67950

Other (OTH)

AF:

0.00190

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.000759

Hom.:

Bravo

AF:

0.000846

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SOCS1: BS1, BS2 -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.35

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over