rs200232916

Variant names:

• chr5-139477524-G-T
• rs200232916
• NM_198282.4:c.760-9C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-139477524-G-T
• chr5-139477524-G-A
• chr5-139477524-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_198282.4(STING1):​c.760-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,612,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (0 hom.)
• Consequence: STING1 NM_198282.4 intron
• Scores: Splicing: ADA: 0.001314
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0530
• Publications: 0 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, 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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-139477524-G-T is Benign according to our data. Variant chr5-139477524-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 541982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000394 (60/152296) while in subpopulation NFE AF = 0.00075 (51/68028). AF 95% confidence interval is 0.000585. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STING1	NM_198282.4	MANE Select	c.760-9C>A		intron	N/A	NP_938023.1	Q86WV6
	STING1	NM_001301738.2		c.759+746C>A		intron	N/A	NP_001288667.1	J3QTB1
	STING1	NM_001367258.1		c.403-9C>A		intron	N/A	NP_001354187.1	A0A494C0W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STING1	ENST00000330794.9	TSL:1 MANE Select	c.760-9C>A		intron	N/A	ENSP00000331288.4	Q86WV6
	STING1	ENST00000512606.6	TSL:1	n.996-9C>A		intron	N/A
	STING1	ENST00000651699.1		c.760-9C>A		intron	N/A	ENSP00000499166.1	Q86WV6

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000345 AC: 86 AN: 249018 AF XY: 0.000357

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000561

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000637 AC: 930 AN: 1460128 Hom.: 0 Cov.: 32 AF XY: 0.000595 AC XY: 432 AN XY: 726266

African (AFR) AF: 0.000120 AC: 4 AN: 33430

American (AMR) AF: 0.000404 AC: 18 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000105 AC: 9 AN: 86102

European-Finnish (FIN) AF: 0.000188 AC: 10 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000760 AC: 844 AN: 1111014

Other (OTH) AF: 0.000746 AC: 45 AN: 60328

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74464

African (AFR) AF: 0.000120 AC: 5 AN: 41554

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000384 Hom.: 0

Bravo AF: 0.000310

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	STING-associated vasculopathy with onset in infancy (2)
-	-	1	Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		-0.053

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.034
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: rs200232916; hg19: chr5-138857109;