rs114583092

chr11-4023999-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382567.1(STIM1):c.385+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,605,146 control chromosomes in the GnomAD database, including 814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (411 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (403 hom.)
• Consequence: STIM1 NM_001382567.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.315

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-4023999-C-T is Benign according to our data. Variant chr11-4023999-C-T is described in ClinVar as [Benign]. Clinvar id is 258977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1	c.385+12C>T		intron_variant		ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2	c.385+12C>T		intron_variant		5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6342 AN: 152028 Hom.: 408 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.0368

GnomAD3 exomes AF: 0.0128 AC: 3211 AN: 251112 Hom.: 156 AF XY: 0.0100 AC XY: 1357 AN XY: 135732

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.00546

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00340

Gnomad FIN exome AF: 0.000234

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00946

GnomAD4 exome AF: 0.00670 AC: 9735 AN: 1453000 Hom.: 403 Cov.: 27 AF XY: 0.00612 AC XY: 4429 AN XY: 723440

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0114

Gnomad4 ASJ exome AF: 0.00586

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00361

Gnomad4 FIN exome AF: 0.000695

Gnomad4 NFE exome AF: 0.00282

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0417 AC: 6351 AN: 152146 Hom.: 411 Cov.: 32 AF XY: 0.0396 AC XY: 2948 AN XY: 74368

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.00865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00316

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0202 Hom.: 34

Bravo AF: 0.0473

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2016	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. -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	14
Dann	Benign	0.69

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

Other links and lift over

dbSNP: rs114583092; hg19: chr11-4045229;