rs11554776

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STING1	NM_198282.4 link	c.212G>A	p.Arg71His	missense_variant	Exon 3 of 8	ENST00000330794.9	NP_938023.1	Q86WV6
STING1	NM_001301738.2 link	c.212G>A	p.Arg71His	missense_variant	Exon 3 of 7		NP_001288667.1	J3QTB1V5V0K2
STING1	NM_001367258.1 link	c.-130-151G>A		intron_variant	Intron 2 of 6		NP_001354187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9 link	c.212G>A	p.Arg71His	missense_variant	Exon 3 of 8	1	NM_198282.4	ENSP00000331288.4		Q86WV6

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

GnomAD3 exomes

AF:

0.195

AC:

48707

AN:

250218

Hom.:

6198

AF XY:

0.190

AC XY:

25803

AN XY:

135532

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 SAS exome

AF:

0.220

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

Gnomad4 AFR exome

AF:

0.0309

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.222

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.138

AC:

20933

AN:

152194

Hom.:

2103

Cov.:

AF XY:

0.145

AC XY:

10796

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0345

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.145

Hom.:

3239

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

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 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

not provided

Benign: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: 21248775, 27927967, 24204993, 29632140) -

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

0.076

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.056

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.76

T;.

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.76

N;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.021

Sift

Benign

0.24

T;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0080

B;.

Vest4

0.014

MPC

0.60

ClinPred

0.0030

GERP RS

1.8

Varity_R

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over