chr5-139476277-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_198282.4(STING1):c.1124G>T(p.Arg375Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,588,738 control chromosomes in the GnomAD database, including 5 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00037 ( 5 hom. )

Consequence

STING1
NM_198282.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.05

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 Does not affect ability to activate IRF3. Abolished ability to induce the production of type I interferon. (size 0) in uniprot entity STING_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0076682866).

BP6

Variant 5-139476277-C-A is Benign according to our data. Variant chr5-139476277-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 719130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000296 (45/152192) while in subpopulation EAS AF= 0.00774 (40/5168). AF 95% confidence interval is 0.00584. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STING1	NM_198282.4 link	c.1124G>T	p.Arg375Leu	missense_variant	Exon 8 of 8	ENST00000330794.9	NP_938023.1	Q86WV6
STING1	NM_001367258.1 link	c.767G>T	p.Arg256Leu	missense_variant	Exon 7 of 7		NP_001354187.1
STING1	NM_001301738.2 link	c.*85G>T		3_prime_UTR_variant	Exon 7 of 7		NP_001288667.1	J3QTB1V5V0K2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9 link	c.1124G>T	p.Arg375Leu	missense_variant	Exon 8 of 8	1	NM_198282.4	ENSP00000331288.4		Q86WV6

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00792

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000784

AC:

167

AN:

213096

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

114454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0102

Gnomad SAS exome

AF:

0.0000737

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000431

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000367

AC:

527

AN:

1436546

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

259

AN XY:

712626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000149

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0117

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.0000155

Gnomad4 OTH exome

AF:

0.000674

GnomAD4 genome

AF:

0.000296

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00774

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000280

ExAC

AF:

0.000735

AC:

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

STING-associated vasculopathy with onset in infancy

Benign:2

Jan 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Benign

0.069

Eigen_PC

Benign

-0.025

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0077

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

REVEL

Benign

0.10

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.61

MVP

0.49

MPC

1.5

ClinPred

0.21

GERP RS

3.5

Varity_R

0.53

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