5-139477397-C-T

Position:

chr5-139477397-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The ENST00000330794.9(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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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
ENST00000330794.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.38

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 -18 ACMG points.

PM1

In a helix (size 20) in uniprot entity STING_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in ENST00000330794.9

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 id 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/exons	MANE	Protein
STING1	NM_198282.4 linkuse as main transcript	c.878G>A	p.Arg293Gln	missense_variant	7/8	ENST00000330794.9	NP_938023.1
STING1	NM_001367258.1 linkuse as main transcript	c.521G>A	p.Arg174Gln	missense_variant	6/7		NP_001354187.1
STING1	NM_001301738.2 linkuse as main transcript	c.759+873G>A		intron_variant			NP_001288667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9 linkuse as main transcript	c.878G>A	p.Arg293Gln	missense_variant	7/8	1	NM_198282.4	ENSP00000331288	P1

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

GnomAD3 exomes

AF:

0.212

AC:

53352

AN:

251290

Hom.:

6997

AF XY:

0.203

AC XY:

27604

AN XY:

135804

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 SAS exome

AF:

0.221

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

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.433

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.204

AC:

31097

AN:

152124

Hom.:

3698

Cov.:

AF XY:

0.209

AC XY:

15571

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.300

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.236

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.160

Hom.:

4173

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2018

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

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 14, 2022

- -

STING-associated vasculopathy with onset in infancy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

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

MutationTaster

Benign

0.0000045

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

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

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