Genetic Variant STING1:p.Pro11Pro (chr5-139481672-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.870

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

STING-associated vasculopathy with onset in infancy
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, Orphanet
familial chilblain lupus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

STING1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 Homozygotes in GnomAd4 at 4 AD,AR 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

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	Q86WV6
STING1	NM_001301738.2		c.33G>A	p.Pro11Pro	synonymous	Exon 3 of 7	NP_001288667.1	J3QTB1
STING1	NM_001367258.1		c.-130-330G>A		intron	N/A	NP_001354187.1	A0A494C0W5

Ensembl Transcripts

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	Q86WV6
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	Q86WV6

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152070

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.00268

AC XY:

1939

AN XY:

724156

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

33396

American (AMR)

AF:

0.000762

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00157

AC:

AN:

26094

East Asian (EAS)

AF:

0.000101

AC:

AN:

39494

South Asian (SAS)

AF:

0.0207

AC:

1784

AN:

86184

European-Finnish (FIN)

AF:

0.0000570

AC:

AN:

52662

Middle Eastern (MID)

AF:

0.0148

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000720

AC:

799

AN:

1109100

Other (OTH)

AF:

0.00246

AC:

148

AN:

60146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

150

300

451

601

751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00186

AC:

283

AN:

152188

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41516

American (AMR)

AF:

0.00105

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0230

AC:

111

AN:

4820

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

67988

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.00125

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00101

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autoinflammatory syndrome (1)

STING-associated vasculopathy with onset in infancy (1)

STING1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.2

(source)

DANN

Benign

0.59

PhyloP100

-0.87

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over