11-3855844-C-T

Position:

• chr11-3855844-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.-427C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 201,524 control chromosomes in the GnomAD database, including 16,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11773 hom., cov: 35)
  • Exomes 𝑓: 0.42 (4844 hom.)
• Consequence: STIM1 NM_001382567.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.959

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=-0.8).
• BP6: Variant 11-3855844-C-T is Benign according to our data. Variant chr11-3855844-C-T is described in ClinVar as [Benign]. Clinvar id is 1232342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1	c.-427C>T		5_prime_UTR_variant	1/13	ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2	c.-427C>T		5_prime_UTR_variant	1/13	5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59378 AN: 151848 Hom.: 11760 Cov.: 35

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.418 AC: 20710 AN: 49560 Hom.: 4844 Cov.: 0 AF XY: 0.428 AC XY: 11571 AN XY: 27044

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.453

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.391 AC: 59434 AN: 151964 Hom.: 11773 Cov.: 35 AF XY: 0.397 AC XY: 29492 AN XY: 74270

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.362

Alfa AF: 0.327 Hom.: 1442

Bravo AF: 0.385

Asia WGS AF: 0.503 AC: 1745 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10835206; hg19: chr11-3877074;