rs11554776

Variant names:

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.212G>A(p.Arg71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,470 control chromosomes in the GnomAD database, including 22,403 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.14 ( 2103 hom., cov: 32)

Exomes 𝑓: 0.15 ( 20300 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0650

Publications

91 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=0.0038261712).

BP6

Variant 5-139481493-C-T is Benign according to our data. Variant chr5-139481493-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STING1	NM_198282.4	MANE Select	c.212G>A	p.Arg71His	missense	Exon 3 of 8	NP_938023.1
STING1	NM_001301738.2		c.212G>A	p.Arg71His	missense	Exon 3 of 7	NP_001288667.1
STING1	NM_001367258.1		c.-130-151G>A		intron	N/A	NP_001354187.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STING1	ENST00000330794.9	TSL:1 MANE Select	c.212G>A	p.Arg71His	missense	Exon 3 of 8	ENSP00000331288.4
STING1	ENST00000512606.6	TSL:1	n.313G>A		non_coding_transcript_exon	Exon 2 of 6
STING1	ENST00000651699.1		c.212G>A	p.Arg71His	missense	Exon 2 of 7	ENSP00000499166.1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20905

AN:

152076

Hom.:

2089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0345

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.165

GnomAD2 exomes

AF:

0.195

AC:

48707

AN:

250218

AF XY:

0.190

show subpopulations

Gnomad AFR exome

AF:

0.0334

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.151

AC:

221284

AN:

1461276

Hom.:

20300

Cov.:

AF XY:

0.153

AC XY:

111147

AN XY:

726952

show subpopulations

African (AFR)

AF:

0.0309

AC:

1034

AN:

33478

American (AMR)

AF:

0.341

AC:

15244

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

5424

AN:

26094

East Asian (EAS)

AF:

0.431

AC:

17109

AN:

39688

South Asian (SAS)

AF:

0.222

AC:

19143

AN:

86236

European-Finnish (FIN)

AF:

0.155

AC:

8239

AN:

53146

Middle Eastern (MID)

AF:

0.186

AC:

1073

AN:

5764

European-Non Finnish (NFE)

AF:

0.130

AC:

144313

AN:

1111782

Other (OTH)

AF:

0.161

AC:

9705

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10238

20476

30714

40952

51190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5512

11024

16536

22048

27560

<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:

0.138

AC:

20933

AN:

152194

Hom.:

2103

Cov.:

AF XY:

0.145

AC XY:

10796

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0345

AC:

1433

AN:

41536

American (AMR)

AF:

0.277

AC:

4231

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

713

AN:

3466

East Asian (EAS)

AF:

0.413

AC:

2134

AN:

5162

South Asian (SAS)

AF:

0.234

AC:

1131

AN:

4832

European-Finnish (FIN)

AF:

0.153

AC:

1627

AN:

10608

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9167

AN:

67988

Other (OTH)

AF:

0.169

AC:

356

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

871

1741

2612

3482

4353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<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:

0.142

Hom.:

4605

Bravo

AF:

0.142

TwinsUK

AF:

0.141

AC:

523

ALSPAC

AF:

0.128

AC:

494

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.140

AC:

1200

ExAC

AF:

0.182

AC:

22102

Asia WGS

AF:

0.324

AC:

1124

AN:

3478

EpiCase

AF:

0.148

EpiControl

AF:

0.147

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autoinflammatory syndrome (1)

not provided (1)

not specified (1)

STING-associated vasculopathy with onset in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.056

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.76

PhyloP100

-0.065

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.83

REVEL

Benign

0.021

Sift

Benign

0.24

Sift4G

Benign

0.60

Polyphen

0.0080

Vest4

0.014

MPC

0.60

ClinPred

0.0030

GERP RS

1.8

PromoterAI

-0.0026

Neutral

(source)

Varity_R

0.15

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over