Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198282.4(STING1):c.937G>A(p.Ala313Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,613,772 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 19 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.83

Publications

10 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=0.008134723).

BP6

Variant 5-139477338-C-T is Benign according to our data. Variant chr5-139477338-C-T is described in ClinVar as Benign. ClinVar VariationId is 475211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00729 (1110/152322) while in subpopulation AFR AF = 0.021 (875/41580). AF 95% confidence interval is 0.0199. There are 16 homozygotes in GnomAd4. There are 526 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1110 AD gene.

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.937G>A	p.Ala313Thr	missense	Exon 7 of 8	NP_938023.1
STING1	NM_001367258.1		c.580G>A	p.Ala194Thr	missense	Exon 6 of 7	NP_001354187.1
STING1	NM_001301738.2		c.760-884G>A		intron	N/A	NP_001288667.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STING1	ENST00000330794.9	TSL:1 MANE Select	c.937G>A	p.Ala313Thr	missense	Exon 7 of 8	ENSP00000331288.4
STING1	ENST00000512606.6	TSL:1	n.1173G>A		non_coding_transcript_exon	Exon 5 of 6
STING1	ENST00000651699.1		c.937G>A	p.Ala313Thr	missense	Exon 6 of 7	ENSP00000499166.1

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

1110

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00911

GnomAD2 exomes

AF:

0.00303

AC:

759

AN:

250120

AF XY:

0.00271

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.00679

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00176

AC:

2572

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1283

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.0210

AC:

703

AN:

33474

American (AMR)

AF:

0.00559

AC:

250

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00728

AC:

190

AN:

26114

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.000789

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.000768

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.0126

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.000868

AC:

965

AN:

1111920

Other (OTH)

AF:

0.00467

AC:

282

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

132

263

395

526

658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00729

AC:

1110

AN:

152322

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

526

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0210

AC:

875

AN:

41580

American (AMR)

AF:

0.00530

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00135

AC:

AN:

68024

Other (OTH)

AF:

0.00901

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00326

Hom.:

Bravo

AF:

0.00814

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0172

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00333

AC:

404

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00219

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autoinflammatory syndrome (1)

STING-associated vasculopathy with onset in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0081

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.29

REVEL

Benign

0.034

Sift

Benign

0.16

Sift4G

Uncertain

0.049

Polyphen

0.010

Vest4

0.14

MVP

0.21

MPC

0.46

ClinPred

0.013

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.19

Mutation Taster

=89/11

polymorphism

(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

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

rs140837017

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over