5-139477397-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_198282.4(STING1):c.878G>A(p.Arg293Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,894 control chromosomes in the GnomAD database, including 25,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R293W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3698 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21991 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.38

Publications

129 publications found

Variant links:

Genes affected

STING1 (HGNC:27962): (stimulator of interferon response cGAMP interactor 1) This gene encodes a five transmembrane protein that functions as a major regulator of the innate immune response to viral and bacterial infections. The encoded protein is a pattern recognition receptor that detects cytosolic nucleic acids and transmits signals that activate type I interferon responses. The encoded protein has also been shown to play a role in apoptotic signaling by associating with type II major histocompatibility complex. Mutations in this gene are the cause of infantile-onset STING-associated vasculopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

STING1 Gene-Disease associations (from GenCC):

STING-associated vasculopathy with onset in infancy
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
familial chilblain lupus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

STING1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a helix (size 20) in uniprot entity STING_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_198282.4

BP4

Computational evidence support a benign effect (MetaRNN=0.0029341578).

BP6

Variant 5-139477397-C-T is Benign according to our data. Variant chr5-139477397-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STING1	NM_198282.4 link	c.878G>A	p.Arg293Gln	missense_variant	Exon 7 of 8	ENST00000330794.9	NP_938023.1	Q86WV6
STING1	NM_001367258.1 link	c.521G>A	p.Arg174Gln	missense_variant	Exon 6 of 7		NP_001354187.1
STING1	NM_001301738.2 link	c.759+873G>A		intron_variant	Intron 6 of 6		NP_001288667.1	J3QTB1V5V0K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9 link	c.878G>A	p.Arg293Gln	missense_variant	Exon 7 of 8	1	NM_198282.4	ENSP00000331288.4		Q86WV6

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31037

AN:

152006

Hom.:

3678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.299

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.212

AC:

53352

AN:

251290

AF XY:

0.203

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.159

AC:

231692

AN:

1461770

Hom.:

21991

Cov.:

AF XY:

0.159

AC XY:

115587

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.266

AC:

8915

AN:

33472

American (AMR)

AF:

0.354

AC:

15844

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5401

AN:

26134

East Asian (EAS)

AF:

0.433

AC:

17190

AN:

39684

South Asian (SAS)

AF:

0.223

AC:

19230

AN:

86248

European-Finnish (FIN)

AF:

0.156

AC:

8321

AN:

53414

Middle Eastern (MID)

AF:

0.198

AC:

1139

AN:

5762

European-Non Finnish (NFE)

AF:

0.130

AC:

145016

AN:

1111956

Other (OTH)

AF:

0.176

AC:

10636

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

10357

20713

31070

41426

51783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5658

11316

16974

22632

28290

<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:

0.204

AC:

31097

AN:

152124

Hom.:

3698

Cov.:

AF XY:

0.209

AC XY:

15571

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.266

AC:

11048

AN:

41470

American (AMR)

AF:

0.300

AC:

4592

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3470

East Asian (EAS)

AF:

0.415

AC:

2145

AN:

5172

South Asian (SAS)

AF:

0.236

AC:

1137

AN:

4824

European-Finnish (FIN)

AF:

0.153

AC:

1625

AN:

10596

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9244

AN:

67990

Other (OTH)

AF:

0.215

AC:

453

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1237

2473

3710

4946

6183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<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:

0.164

Hom.:

8820

Bravo

AF:

0.218

TwinsUK

AF:

0.141

AC:

524

ALSPAC

AF:

0.129

AC:

497

ESP6500AA

AF:

0.266

AC:

1172

ESP6500EA

AF:

0.141

AC:

1214

ExAC

AF:

0.204

AC:

24822

Asia WGS

AF:

0.336

AC:

1169

AN:

3478

EpiCase

AF:

0.149

EpiControl

AF:

0.148

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

not provided

Benign:1

Aug 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29632140, 30368497, 24204993, 27927967, 21248775) -

Autoinflammatory syndrome

Benign:1

Jan 14, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

STING-associated vasculopathy with onset in infancy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

2.9

PhyloP100

3.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.1

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.12

MPC

0.86

ClinPred

0.041

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.88

Mutation Taster

=84/16

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over