rs1131769

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198282.4(STING1):c.695A>G(p.His232Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,613,916 control chromosomes in the GnomAD database, including 615,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57719 hom., cov: 31)

Exomes 𝑓: 0.87 ( 558127 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 2.21

Publications

106 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4088237E-6).

BP6

Variant 5-139478334-T-C is Benign according to our data. Variant chr5-139478334-T-C is described in ClinVar as Benign. ClinVar VariationId is 403550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STING1	NM_198282.4 link	c.695A>G	p.His232Arg	missense_variant	Exon 6 of 8	ENST00000330794.9	NP_938023.1	Q86WV6
STING1	NM_001301738.2 link	c.695A>G	p.His232Arg	missense_variant	Exon 6 of 7		NP_001288667.1	J3QTB1V5V0K2
STING1	NM_001367258.1 link	c.338A>G	p.His113Arg	missense_variant	Exon 5 of 7		NP_001354187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9 link	c.695A>G	p.His232Arg	missense_variant	Exon 6 of 8	1	NM_198282.4	ENSP00000331288.4		Q86WV6

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132374

AN:

151992

Hom.:

57673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.881

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.857

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.881

Gnomad SAS

AF:

0.905

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.874

GnomAD2 exomes

AF:

0.876

AC:

220195

AN:

251454

AF XY:

0.875

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.887

Gnomad ASJ exome

AF:

0.855

Gnomad EAS exome

AF:

0.880

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.866

Gnomad OTH exome

AF:

0.877

GnomAD4 exome

AF:

0.874

AC:

1276983

AN:

1461806

Hom.:

558127

Cov.:

AF XY:

0.874

AC XY:

635860

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.890

AC:

29792

AN:

33474

American (AMR)

AF:

0.885

AC:

39576

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

22331

AN:

26136

East Asian (EAS)

AF:

0.873

AC:

34661

AN:

39696

South Asian (SAS)

AF:

0.909

AC:

78423

AN:

86254

European-Finnish (FIN)

AF:

0.864

AC:

46168

AN:

53416

Middle Eastern (MID)

AF:

0.878

AC:

5064

AN:

5766

European-Non Finnish (NFE)

AF:

0.871

AC:

968167

AN:

1111948

Other (OTH)

AF:

0.874

AC:

52801

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9210

18421

27631

36842

46052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21314

42628

63942

85256

106570

<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:

0.871

AC:

132478

AN:

152110

Hom.:

57719

Cov.:

AF XY:

0.869

AC XY:

64615

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.881

AC:

36576

AN:

41516

American (AMR)

AF:

0.857

AC:

13075

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2964

AN:

3468

East Asian (EAS)

AF:

0.882

AC:

4549

AN:

5160

South Asian (SAS)

AF:

0.905

AC:

4360

AN:

4818

European-Finnish (FIN)

AF:

0.857

AC:

9064

AN:

10578

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.869

AC:

59089

AN:

67992

Other (OTH)

AF:

0.875

AC:

1849

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

894

1787

2681

3574

4468

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:

0.868

Hom.:

198028

Bravo

AF:

0.871

TwinsUK

AF:

0.867

AC:

3213

ALSPAC

AF:

0.865

AC:

3332

ESP6500AA

AF:

0.872

AC:

3841

ESP6500EA

AF:

0.869

AC:

7475

ExAC

AF:

0.876

AC:

106354

Asia WGS

AF:

0.873

AC:

3037

AN:

3478

EpiCase

AF:

0.866

EpiControl

AF:

0.862

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

STING-associated vasculopathy with onset in infancy

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 14, 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 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1Other:1

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23707065, 24204993, 33154747, 31866997) -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.066

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.26

T;.

MetaRNN

Benign

0.0000014

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.8

N;.

PhyloP100

2.2

PrimateAI

Benign

0.39

PROVEAN

Benign

4.5

N;N

REVEL

Benign

0.083

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.036

MPC

0.58

ClinPred

0.0023

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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