rs78233829

Variant names:

• chr5-139478340-C-G
• rs78233829
• NM_198282.4:c.689G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-139478340-C-G
• chr5-139478340-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1 BP4_Strong BP6_Very_Strong BA1

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. 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. 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.547
• Publications: 90 publications found

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• PM1: In a mutagenesis_site Renders the enzyme sensitive 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 VariationId 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 rank	MANE	Protein	UniProt
STING1	NM_198282.4	c.689G>C	p.Gly230Ala	missense_variant	Exon 6 of 8	ENST00000330794.9	NP_938023.1
STING1	NM_001301738.2	c.689G>C	p.Gly230Ala	missense_variant	Exon 6 of 7		NP_001288667.1
STING1	NM_001367258.1	c.332G>C	p.Gly111Ala	missense_variant	Exon 5 of 7		NP_001354187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9	c.689G>C	p.Gly230Ala	missense_variant	Exon 6 of 8	1	NM_198282.4	ENSP00000331288.4

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29935 AN: 151880 Hom.: 3391 Cov.: 31

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

GnomAD2 exomes AF: 0.212 AC: 53220 AN: 251466 AF XY: 0.203

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 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.: 36 AF XY: 0.159 AC XY: 115566 AN XY: 727194

African (AFR) AF: 0.239 AC: 8012 AN: 33474

American (AMR) AF: 0.359 AC: 16034 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 5454 AN: 26136

East Asian (EAS) AF: 0.435 AC: 17251 AN: 39692

South Asian (SAS) AF: 0.225 AC: 19433 AN: 86250

European-Finnish (FIN) AF: 0.156 AC: 8310 AN: 53416

Middle Eastern (MID) AF: 0.199 AC: 1147 AN: 5768

European-Non Finnish (NFE) AF: 0.131 AC: 145185 AN: 1111924

Other (OTH) AF: 0.175 AC: 10562 AN: 60390

GnomAD4 genome AF: 0.197 AC: 29985 AN: 151998 Hom.: 3406 Cov.: 31 AF XY: 0.202 AC XY: 15034 AN XY: 74274

African (AFR) AF: 0.238 AC: 9874 AN: 41460

American (AMR) AF: 0.304 AC: 4640 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2142 AN: 5156

South Asian (SAS) AF: 0.238 AC: 1146 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1619 AN: 10542

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9260 AN: 67974

Other (OTH) AF: 0.210 AC: 443 AN: 2110

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

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 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. 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: 27927967, 24204993, 29632140) -

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	0.056
BayesDel_addAF	Benign	-0.81	T
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	N
LIST_S2	Benign	0.13	T;.
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.0	N;.
PhyloP100		0.55
PrimateAI	Benign	0.27	T
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	T
GERP RS		0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.098
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78233829; hg19: chr5-138857925; COSMIC: COSV58172624; COSMIC: COSV58172624;