NM_001382567.1:c.1474+17C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382567.1(STIM1):c.1474+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 1,605,604 control chromosomes in the GnomAD database, including 653,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.81 ( 52079 hom., cov: 34)

Exomes 𝑓: 0.91 ( 601810 hom. )

Consequence

STIM1
NM_001382567.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.162

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

myopathy, tubular aggregate, 1
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Stormorken syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
tubular aggregate myopathy
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
combined immunodeficiency due to STIM1 deficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

STIM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-4083515-C-G is Benign according to our data. Variant chr11-4083515-C-G is described in ClinVar as Benign. ClinVar VariationId is 258971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382567.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STIM1	NM_001382567.1	MANE Select	c.1474+17C>G	intron	N/A	NP_001369496.1
STIM1	NM_001382573.1		c.*9C>G	3_prime_UTR	Exon 10 of 10	NP_001369502.1
STIM1	NM_001277961.3		c.1474+17C>G	intron	N/A	NP_001264890.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STIM1	ENST00000526596.2	TSL:5 MANE Select	c.1474+17C>G	intron	N/A	ENSP00000433266.2
STIM1	ENST00000616714.4	TSL:1	c.1474+17C>G	intron	N/A	ENSP00000478059.1
STIM1	ENST00000300737.8	TSL:1	c.1474+17C>G	intron	N/A	ENSP00000300737.4

Frequencies

GnomAD3 genomes

AF:

0.812

AC:

123469

AN:

152094

Hom.:

52060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.868

Gnomad EAS

AF:

0.953

Gnomad SAS

AF:

0.935

Gnomad FIN

AF:

0.915

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.912

Gnomad OTH

AF:

0.838

GnomAD2 exomes

AF:

0.894

AC:

209952

AN:

234868

AF XY:

0.900

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.941

Gnomad ASJ exome

AF:

0.863

Gnomad EAS exome

AF:

0.949

Gnomad FIN exome

AF:

0.908

Gnomad NFE exome

AF:

0.909

Gnomad OTH exome

AF:

0.898

GnomAD4 exome

AF:

0.908

AC:

1319467

AN:

1453392

Hom.:

601810

Cov.:

AF XY:

0.909

AC XY:

656982

AN XY:

722502

show subpopulations

African (AFR)

AF:

0.531

AC:

17685

AN:

33298

American (AMR)

AF:

0.935

AC:

40279

AN:

43072

Ashkenazi Jewish (ASJ)

AF:

0.862

AC:

22402

AN:

25976

East Asian (EAS)

AF:

0.960

AC:

37776

AN:

39346

South Asian (SAS)

AF:

0.935

AC:

79691

AN:

85276

European-Finnish (FIN)

AF:

0.915

AC:

48468

AN:

52992

Middle Eastern (MID)

AF:

0.858

AC:

4935

AN:

5752

European-Non Finnish (NFE)

AF:

0.916

AC:

1014744

AN:

1107574

Other (OTH)

AF:

0.890

AC:

53487

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

5754

11509

17263

23018

28772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21400

42800

64200

85600

107000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.812

AC:

123528

AN:

152212

Hom.:

52079

Cov.:

AF XY:

0.815

AC XY:

60691

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.551

AC:

22841

AN:

41468

American (AMR)

AF:

0.890

AC:

13617

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

3014

AN:

3472

East Asian (EAS)

AF:

0.953

AC:

4943

AN:

5186

South Asian (SAS)

AF:

0.935

AC:

4516

AN:

4828

European-Finnish (FIN)

AF:

0.915

AC:

9719

AN:

10620

Middle Eastern (MID)

AF:

0.847

AC:

249

AN:

294

European-Non Finnish (NFE)

AF:

0.912

AC:

62046

AN:

68020

Other (OTH)

AF:

0.837

AC:

1764

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1005

2009

3014

4018

5023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

868

1736

2604

3472

4340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.854

Hom.:

6767

Bravo

AF:

0.795

Asia WGS

AF:

0.921

AC:

3204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Oct 19, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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.

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported.

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Combined immunodeficiency due to STIM1 deficiency

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Stormorken syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Myopathy, tubular aggregate, 1

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.4

(source)

DANN

Benign

0.61

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over