rs1272445335

Variant names:

• chr5-139476279-G-A
• rs1272445335
• NM_198282.4:c.1122C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_198282.4(STING1):​c.1122C>T​(p.Leu374Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STING1 NM_198282.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.196
• 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 Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• familial chilblain lupus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 5-139476279-G-A is Benign according to our data. Variant chr5-139476279-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3724034.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.196 with no splicing effect.

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.1122C>T	p.Leu374Leu	synonymous	Exon 8 of 8	NP_938023.1	Q86WV6
	STING1	NM_001367258.1		c.765C>T	p.Leu255Leu	synonymous	Exon 7 of 7	NP_001354187.1	A0A494C0W5
	STING1	NM_001301738.2		c.*83C>T		3_prime_UTR	Exon 7 of 7	NP_001288667.1	J3QTB1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STING1	ENST00000330794.9	TSL:1 MANE Select	c.1122C>T	p.Leu374Leu	synonymous	Exon 8 of 8	ENSP00000331288.4	Q86WV6
	STING1	ENST00000512606.6	TSL:1	n.1358C>T		non_coding_transcript_exon	Exon 6 of 6
	STING1	ENST00000651699.1		c.1122C>T	p.Leu374Leu	synonymous	Exon 7 of 7	ENSP00000499166.1	Q86WV6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 218832 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		-0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1272445335; hg19: chr5-138855864;