5-139481672-C-T

Variant names:

• chr5-139481672-C-T
• rs149842998
• NM_198282.4:c.33G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_198282.4(STING1):​c.33G>A​(p.Pro11Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,609,638 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (34 hom.)
• Consequence: STING1 NM_198282.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.870
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-139481672-C-T is Benign according to our data. Variant chr5-139481672-C-T is described in ClinVar as Benign. ClinVar VariationId is 541981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.87 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00186 (283/152188) while in subpopulation SAS AF = 0.023 (111/4820). AF 95% confidence interval is 0.0196. There are 4 homozygotes in GnomAd4. There are 167 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 283 AD gene.

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.33G>A	p.Pro11Pro	synonymous	Exon 3 of 8	NP_938023.1
	STING1	NM_001301738.2		c.33G>A	p.Pro11Pro	synonymous	Exon 3 of 7	NP_001288667.1
	STING1	NM_001367258.1		c.-130-330G>A		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.33G>A	p.Pro11Pro	synonymous	Exon 3 of 8	ENSP00000331288.4
	STING1	ENST00000512606.6	TSL:1	n.134G>A		non_coding_transcript_exon	Exon 2 of 6
	STING1	ENST00000651699.1		c.33G>A	p.Pro11Pro	synonymous	Exon 2 of 7	ENSP00000499166.1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152070 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00339 AC: 838 AN: 247254 AF XY: 0.00450

Gnomad AFR exome AF: 0.000260

Gnomad AMR exome AF: 0.000755

Gnomad ASJ exome AF: 0.00191

Gnomad EAS exome AF: 0.000328

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000980

Gnomad OTH exome AF: 0.00215

GnomAD4 exome AF: 0.00199 AC: 2906 AN: 1457450 Hom.: 34 Cov.: 33 AF XY: 0.00268 AC XY: 1939 AN XY: 724156

African (AFR) AF: 0.000240 AC: 8 AN: 33396

American (AMR) AF: 0.000762 AC: 34 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 41 AN: 26094

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39494

South Asian (SAS) AF: 0.0207 AC: 1784 AN: 86184

European-Finnish (FIN) AF: 0.0000570 AC: 3 AN: 52662

Middle Eastern (MID) AF: 0.0148 AC: 85 AN: 5756

European-Non Finnish (NFE) AF: 0.000720 AC: 799 AN: 1109100

Other (OTH) AF: 0.00246 AC: 148 AN: 60146

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152188 Hom.: 4 Cov.: 31 AF XY: 0.00224 AC XY: 167 AN XY: 74404

African (AFR) AF: 0.000265 AC: 11 AN: 41516

American (AMR) AF: 0.00105 AC: 16 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 67988

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00125

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

STING1-related disorder Benign:1

Jan 28, 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).

Autoinflammatory syndrome Benign:1

Jun 11, 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

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.87
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs149842998; hg19: chr5-138861257; COSMIC: COSV58172915; COSMIC: COSV58172915;