rs2304891

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001382567.1(STIM1):c.1080A>G(p.Gln360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,613,296 control chromosomes in the GnomAD database, including 246,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16939 hom., cov: 32)

Exomes 𝑓: 0.55 ( 229336 hom. )

Consequence

STIM1
NM_001382567.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

STIM1 (HGNC:11386): (stromal interaction molecule 1) This gene encodes a type 1 transmembrane protein that mediates Ca2+ influx after depletion of intracellular Ca2+ stores by gating of store-operated Ca2+ influx channels (SOCs). It is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocrotical carcinoma, and lung, ovarian, and breast cancer. This gene may play a role in malignancies and disease that involve this region, as well as early hematopoiesis, by mediating attachment to stromal cells. Mutations in this gene are associated with fatal classic Kaposi sarcoma, immunodeficiency due to defects in store-operated calcium entry (SOCE) in fibroblasts, ectodermal dysplasia and tubular aggregate myopathy. This gene is oriented in a head-to-tail configuration with the ribonucleotide reductase 1 gene (RRM1), with the 3' end of this gene situated 1.6 kb from the 5' end of the RRM1 gene. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

STIM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-4082294-A-G is Benign according to our data. Variant chr11-4082294-A-G is described in ClinVar as [Benign]. Clinvar id is 258966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-4082294-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.86 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1 linkuse as main transcript	c.1080A>G	p.Gln360=	synonymous_variant	8/13	ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2 linkuse as main transcript	c.1080A>G	p.Gln360=	synonymous_variant	8/13	5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66723

AN:

151966

Hom.:

16951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.566

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.486

GnomAD3 exomes

AF:

0.503

AC:

126143

AN:

250910

Hom.:

33135

AF XY:

0.507

AC XY:

68742

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.162

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.436

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.571

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.554

AC:

810140

AN:

1461212

Hom.:

229336

Cov.:

AF XY:

0.551

AC XY:

400759

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.501

Gnomad4 ASJ exome

AF:

0.554

Gnomad4 EAS exome

AF:

0.486

Gnomad4 SAS exome

AF:

0.450

Gnomad4 FIN exome

AF:

0.497

Gnomad4 NFE exome

AF:

0.584

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.439

AC:

66702

AN:

152084

Hom.:

16939

Cov.:

AF XY:

0.435

AC XY:

32351

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.566

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.477

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.543

Hom.:

50283

Bravo

AF:

0.431

Asia WGS

AF:

0.425

AC:

1476

AN:

3478

EpiCase

AF:

0.568

EpiControl

AF:

0.582

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 62. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 20, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Combined immunodeficiency due to STIM1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Myopathy with tubular aggregates;C1861451:Stormorken syndrome;C2748557:Combined immunodeficiency due to STIM1 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Stormorken syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Myopathy, tubular aggregate, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

Cadd

Benign

6.9

Dann

Benign

0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over