chr5-139481019-C-T

Variant names:

• chr5-139481019-C-T
• rs7380272
• NM_198282.4:c.412-121G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198282.4(STING1):​c.412-121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,190,736 control chromosomes in the GnomAD database, including 19,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3366 hom., cov: 32)
  • Exomes 𝑓: 0.16 (16408 hom.)
• Consequence: STING1 NM_198282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.417
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 5-139481019-C-T is Benign according to our data. Variant chr5-139481019-C-T is described in ClinVar as Benign. ClinVar VariationId is 1239282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STING1	NM_198282.4	MANE Select	c.412-121G>A		intron	N/A	NP_938023.1	Q86WV6
	STING1	NM_001301738.2		c.412-121G>A		intron	N/A	NP_001288667.1	J3QTB1
	STING1	NM_001367258.1		c.55-121G>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.412-121G>A		intron	N/A	ENSP00000331288.4	Q86WV6
	STING1	ENST00000512606.6	TSL:1	n.648-121G>A		intron	N/A
	STING1	ENST00000651699.1		c.412-121G>A		intron	N/A	ENSP00000499166.1	Q86WV6

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29799 AN: 151964 Hom.: 3350 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.159 AC: 165097 AN: 1038654 Hom.: 16408 Cov.: 13 AF XY: 0.160 AC XY: 84545 AN XY: 529218

African (AFR) AF: 0.235 AC: 5774 AN: 24594

American (AMR) AF: 0.351 AC: 12798 AN: 36476

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4483 AN: 21630

East Asian (EAS) AF: 0.431 AC: 15622 AN: 36206

South Asian (SAS) AF: 0.218 AC: 15880 AN: 72696

European-Finnish (FIN) AF: 0.156 AC: 7933 AN: 50970

Middle Eastern (MID) AF: 0.194 AC: 677 AN: 3492

European-Non Finnish (NFE) AF: 0.126 AC: 94039 AN: 746720

Other (OTH) AF: 0.172 AC: 7891 AN: 45870

GnomAD4 genome AF: 0.196 AC: 29850 AN: 152082 Hom.: 3366 Cov.: 32 AF XY: 0.202 AC XY: 14984 AN XY: 74344

African (AFR) AF: 0.236 AC: 9807 AN: 41470

American (AMR) AF: 0.302 AC: 4615 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 714 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2139 AN: 5174

South Asian (SAS) AF: 0.235 AC: 1130 AN: 4818

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10572

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9244 AN: 67998

Other (OTH) AF: 0.208 AC: 437 AN: 2106

Alfa AF: 0.164 Hom.: 6255

Bravo AF: 0.209

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7380272; hg19: chr5-138860604; COSMIC: COSV107369476; COSMIC: COSV107369476;