chr11-4083515-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001382573.1(STIM1):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,605,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STIM1
NM_001382573.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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

STIM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-4083515-C-T is Benign according to our data. Variant chr11-4083515-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2935656.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382573.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STIM1	NM_001382567.1	MANE Select	c.1474+17C>T	intron	N/A	NP_001369496.1	H0YDB2
STIM1	NM_001382573.1		c.*9C>T	3_prime_UTR	Exon 10 of 10	NP_001369502.1
STIM1	NM_001277961.3		c.1474+17C>T	intron	N/A	NP_001264890.1	G0XQ39

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
STIM1	ENST00000526596.2	TSL:5 MANE Select	c.1474+17C>T	intron	N/A	ENSP00000433266.2	H0YDB2
STIM1	ENST00000616714.4	TSL:1	c.1474+17C>T	intron	N/A	ENSP00000478059.1	G0XQ39
STIM1	ENST00000300737.8	TSL:1	c.1474+17C>T	intron	N/A	ENSP00000300737.4	Q13586-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453534

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33310

American (AMR)

AF:

0.00

AC:

AN:

43076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25978

East Asian (EAS)

AF:

0.00

AC:

AN:

39346

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107668

Other (OTH)

AF:

0.00

AC:

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41364

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

6767

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Myopathy with tubular aggregates;C1861451:Stormorken syndrome;C2748557:Combined immunodeficiency due to STIM1 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.4

(source)

DANN

Benign

0.79

PhyloP100

-0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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