Genetic Variant STIM1:c.-84+194dupG (chr11-3855608-C-CG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001382566.1(STIM1):c.-84+194dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 69529 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

STIM1
NM_001382566.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0490

Publications

0 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 links:

STIM1-AS1 (HGNC:40568): (STIM1 antisense RNA 1)

STIM1-AS1 links:

ENSG00000229368 (HGNC:):

ENSG00000229368 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-3855608-C-CG is Benign according to our data. Variant chr11-3855608-C-CG is described in ClinVar as Benign. ClinVar VariationId is 1268800.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382566.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
STIM1	NM_001382566.1	c.-84+194dupG	intron	N/A	NP_001369495.1	A0A8V8TNW0
STIM1	NM_001382575.1	c.-84+874dupG	intron	N/A	NP_001369504.1	A0A8V8TP73
STIM1	NM_001382576.1	c.-84+956dupG	intron	N/A	NP_001369505.1	A0A8V8TP73

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
STIM1	ENST00000698911.1	c.-84+192_-84+193insG	intron	N/A	ENSP00000514025.1	A0A8V8TNW0
STIM1	ENST00000698913.1	c.-84+192_-84+193insG	intron	N/A	ENSP00000514027.1	A0A8V8TP73
STIM1	ENST00000698910.1	c.-220+872_-220+873insG	intron	N/A	ENSP00000514024.1	A0A8V8TMG1

Frequencies

GnomAD3 genomes

AF:

1.00

AC:

139058

AN:

139096

Hom.:

69510

Cov.:

show subpopulations

Gnomad AFR

AF:

1.00

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.998

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

1.00

AC:

139094

AN:

139130

Hom.:

69529

Cov.:

AF XY:

1.00

AC XY:

67337

AN XY:

67354

show subpopulations

African (AFR)

AF:

1.00

AC:

39381

AN:

39386

American (AMR)

AF:

1.00

AC:

14295

AN:

14302

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3336

AN:

3336

East Asian (EAS)

AF:

0.999

AC:

4038

AN:

4042

South Asian (SAS)

AF:

0.998

AC:

4047

AN:

4054

European-Finnish (FIN)

AF:

1.00

AC:

7031

AN:

7032

Middle Eastern (MID)

AF:

1.00

AC:

258

AN:

258

European-Non Finnish (NFE)

AF:

1.00

AC:

63866

AN:

63878

Other (OTH)

AF:

1.00

AC:

1980

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.783

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.0765

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.049

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over