chr11-4091543-C-G

Position:

chr11-4091543-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001382567.1(STIM1):c.1896C>G(p.Pro632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,614,204 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 117 hom. )

Consequence

STIM1
NM_001382567.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.535

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=-0.57).

BP6

Variant 11-4091543-C-G is Benign according to our data. Variant chr11-4091543-C-G is described in ClinVar as [Benign]. Clinvar id is 258974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-4091543-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.535 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00358 (546/152310) while in subpopulation SAS AF= 0.0381 (184/4830). AF 95% confidence interval is 0.0336. There are 2 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM1	NM_001382567.1 linkuse as main transcript	c.1896C>G	p.Pro632=	synonymous_variant	13/13	ENST00000526596.2	NP_001369496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM1	ENST00000526596.2 linkuse as main transcript	c.1896C>G	p.Pro632=	synonymous_variant	13/13	5	NM_001382567.1	ENSP00000433266	P3

Frequencies

GnomAD3 genomes

AF:

0.00360

AC:

548

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0218

Gnomad SAS

AF:

0.0385

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00953

AC:

2396

AN:

251370

Hom.:

AF XY:

0.0107

AC XY:

1453

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0176

Gnomad SAS exome

AF:

0.0454

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00413

AC:

6038

AN:

1461894

Hom.:

117

Cov.:

AF XY:

0.00517

AC XY:

3760

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0159

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.0131

Gnomad4 SAS exome

AF:

0.0430

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000528

Gnomad4 OTH exome

AF:

0.00656

GnomAD4 genome

AF:

0.00358

AC:

546

AN:

152310

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

313

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.0217

Gnomad4 SAS

AF:

0.0381

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00325

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.0

DANN

Benign

0.79

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