5-139481194-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198282.4(STING1):c.376C>A(p.Leu126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,614,230 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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. L126V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 11 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.91

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=0.0062081516).

BP6

Variant 5-139481194-G-T is Benign according to our data. Variant chr5-139481194-G-T is described in ClinVar as [Benign]. Clinvar id is 475205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-139481194-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00345 (525/152364) while in subpopulation AFR AF= 0.0105 (435/41584). AF 95% confidence interval is 0.00965. There are 5 homozygotes in gnomad4. There are 249 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 525 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STING1	NM_198282.4 link	c.376C>A	p.Leu126Ile	missense_variant	Exon 4 of 8	ENST00000330794.9	NP_938023.1	Q86WV6
STING1	NM_001301738.2 link	c.376C>A	p.Leu126Ile	missense_variant	Exon 4 of 7		NP_001288667.1	J3QTB1V5V0K2
STING1	NM_001367258.1 link	c.19C>A	p.Leu7Ile	missense_variant	Exon 3 of 7		NP_001354187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9 link	c.376C>A	p.Leu126Ile	missense_variant	Exon 4 of 8	1	NM_198282.4	ENSP00000331288.4		Q86WV6

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

524

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00125

AC:

313

AN:

251368

Hom.:

AF XY:

0.00110

AC XY:

150

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000493

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000618

AC:

904

AN:

1461866

Hom.:

Cov.:

AF XY:

0.000624

AC XY:

454

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.00169

GnomAD4 genome

AF:

0.00345

AC:

525

AN:

152364

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000718

Hom.:

Bravo

AF:

0.00388

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00137

AC:

166

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

STING1-related disorder

Benign:1

Jan 29, 2024

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STING1: BP4, BS1, BS2 -

Autoinflammatory syndrome

Benign:1

Apr 05, 2021

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 01, 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

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.7

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.59

T;.

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.077

T;T

Polyphen

0.84

P;.

Vest4

0.41

MVP

0.47

MPC

0.61

ClinPred

0.017

GERP RS

2.8

Varity_R

0.22

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