5-139478340-C-G

Position:

chr5-139478340-C-G

Variant summary

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

The NM_198282.4(STING1):c.689G>C(p.Gly230Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,613,770 control chromosomes in the GnomAD database, including 25,333 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G230S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.20 ( 3406 hom., cov: 31)

Exomes 𝑓: 0.16 ( 21927 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.547

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 mutagenesis_site Renders the enzyme senstive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway. (size 0) in uniprot entity STING_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0014354587).

BP6

Variant 5-139478340-C-G is Benign according to our data. Variant chr5-139478340-C-G is described in ClinVar as [Benign]. Clinvar id is 1166568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STING1	NM_198282.4 linkuse as main transcript	c.689G>C	p.Gly230Ala	missense_variant	6/8	ENST00000330794.9
STING1	NM_001301738.2 linkuse as main transcript	c.689G>C	p.Gly230Ala	missense_variant	6/7
STING1	NM_001367258.1 linkuse as main transcript	c.332G>C	p.Gly111Ala	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STING1	ENST00000330794.9 linkuse as main transcript	c.689G>C	p.Gly230Ala	missense_variant	6/8	1	NM_198282.4	P1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29935

AN:

151880

Hom.:

3391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.212

AC:

53220

AN:

251466

Hom.:

6975

AF XY:

0.203

AC XY:

27604

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.419

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.137

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.158

AC:

231388

AN:

1461772

Hom.:

21927

Cov.:

AF XY:

0.159

AC XY:

115566

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.359

Gnomad4 ASJ exome

AF:

0.209

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.156

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.197

AC:

29985

AN:

151998

Hom.:

3406

Cov.:

AF XY:

0.202

AC XY:

15034

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.304

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.415

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.154

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.156

Hom.:

1626

Bravo

AF:

0.210

TwinsUK

AF:

0.141

AC:

524

ALSPAC

AF:

0.129

AC:

498

ESP6500AA

AF:

0.237

AC:

1046

ESP6500EA

AF:

0.142

AC:

1218

ExAC

AF:

0.203

AC:

24660

Asia WGS

AF:

0.338

AC:

1174

AN:

3478

EpiCase

AF:

0.149

EpiControl

AF:

0.149

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

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

STING-associated vasculopathy with onset in infancy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.21

DANN

Benign

0.63

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.13

T;.

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.0

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

2.3

N;N

REVEL

Benign

0.024

Sift

Benign

0.23

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.010

MPC

0.51

ClinPred

0.0073

GERP RS

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.098

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