rs7447927

Variant names:

• chr5-139481561-C-G
• rs7447927
• NM_198282.4:c.144G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-139481561-C-G
• chr5-139481561-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_198282.4(STING1):​c.144G>C​(p.Val48Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,613,522 control chromosomes in the GnomAD database, including 389,177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (25808 hom., cov: 31)
  • Exomes 𝑓: 0.70 (363369 hom.)
• Consequence: STING1 NM_198282.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.115
• Publications: 45 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 -16 ACMG points.

• BP6: Variant 5-139481561-C-G is Benign according to our data. Variant chr5-139481561-C-G is described in ClinVar as Benign. ClinVar VariationId is 403551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STING1	NM_198282.4	MANE Select	c.144G>C	p.Val48Val	synonymous	Exon 3 of 8	NP_938023.1
	STING1	NM_001301738.2		c.144G>C	p.Val48Val	synonymous	Exon 3 of 7	NP_001288667.1
	STING1	NM_001367258.1		c.-130-219G>C		intron	N/A	NP_001354187.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STING1	ENST00000330794.9	TSL:1 MANE Select	c.144G>C	p.Val48Val	synonymous	Exon 3 of 8	ENSP00000331288.4
	STING1	ENST00000512606.6	TSL:1	n.245G>C		non_coding_transcript_exon	Exon 2 of 6
	STING1	ENST00000651699.1		c.144G>C	p.Val48Val	synonymous	Exon 2 of 7	ENSP00000499166.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80730 AN: 151938 Hom.: 25818 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.618 AC: 154729 AN: 250522 AF XY: 0.636

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.492

Gnomad ASJ exome AF: 0.636

Gnomad EAS exome AF: 0.368

Gnomad FIN exome AF: 0.704

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.696 AC: 1016618 AN: 1461466 Hom.: 363369 Cov.: 61 AF XY: 0.698 AC XY: 507161 AN XY: 727054

African (AFR) AF: 0.163 AC: 5460 AN: 33472

American (AMR) AF: 0.491 AC: 21967 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 16543 AN: 26128

East Asian (EAS) AF: 0.368 AC: 14623 AN: 39686

South Asian (SAS) AF: 0.679 AC: 58581 AN: 86258

European-Finnish (FIN) AF: 0.700 AC: 37237 AN: 53198

Middle Eastern (MID) AF: 0.613 AC: 3537 AN: 5768

European-Non Finnish (NFE) AF: 0.737 AC: 819220 AN: 1111874

Other (OTH) AF: 0.653 AC: 39450 AN: 60386

GnomAD4 genome AF: 0.531 AC: 80719 AN: 152056 Hom.: 25808 Cov.: 31 AF XY: 0.529 AC XY: 39319 AN XY: 74330

African (AFR) AF: 0.175 AC: 7255 AN: 41498

American (AMR) AF: 0.487 AC: 7444 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2212 AN: 3468

East Asian (EAS) AF: 0.378 AC: 1952 AN: 5168

South Asian (SAS) AF: 0.660 AC: 3182 AN: 4822

European-Finnish (FIN) AF: 0.693 AC: 7338 AN: 10590

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49403 AN: 67916

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.666 Hom.: 11351

Bravo AF: 0.498

Asia WGS AF: 0.469 AC: 1630 AN: 3478

EpiCase AF: 0.711

EpiControl AF: 0.708

ClinVar

Significance: Benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

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 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 77. Only high quality variants are reported.

STING-associated vasculopathy with onset in infancy Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Other:1

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.91
DANN	Benign	0.35
PhyloP100		-0.12
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7447927; hg19: chr5-138861146; COSMIC: COSV58172685; COSMIC: COSV58172685;