11-3855883-CTCTCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001382567.1(STIM1):c.-370_-366del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 237,122 control chromosomes in the GnomAD database, including 12,371 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7795 hom., cov: 0)
  • Exomes 𝑓: 0.32 (4576 hom.)
• Consequence: STIM1 NM_001382567.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.755

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 -10 ACMG points.

• BP6: Variant 11-3855883-CTCTCT-C is Benign according to our data. Variant chr11-3855883-CTCTCT-C is described in ClinVar as [Benign]. Clinvar id is 1249545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1	c.-370_-366del		5_prime_UTR_variant	1/13	ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2	c.-370_-366del		5_prime_UTR_variant	1/13	5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46144 AN: 151570 Hom.: 7792 Cov.: 0

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.319 AC: 27227 AN: 85434 Hom.: 4576 AF XY: 0.312 AC XY: 14603 AN XY: 46876

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.352

GnomAD4 genome AF: 0.304 AC: 46178 AN: 151688 Hom.: 7795 Cov.: 0 AF XY: 0.303 AC XY: 22461 AN XY: 74122

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.323

Bravo AF: 0.302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3061890; hg19: chr11-3877113;