rs7380272

Positions:

• chr5-139481019-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STING1	NM_198282.4	c.412-121G>A		intron_variant		ENST00000330794.9	NP_938023.1
STING1	NM_001301738.2	c.412-121G>A		intron_variant			NP_001288667.1
STING1	NM_001367258.1	c.55-121G>A		intron_variant			NP_001354187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STING1	ENST00000330794.9	c.412-121G>A		intron_variant		1	NM_198282.4	ENSP00000331288.4

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

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.172

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.208

Alfa AF: 0.156 Hom.: 3474

Bravo AF: 0.209

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs7380272; hg19: chr5-138860604;