11-3855664-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001382567.1(STIM1):c.-607A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 144,910 control chromosomes in the GnomAD database, including 16,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (16166 hom., cov: 33)
  • Exomes 𝑓: 0.51 (20 hom.)
• Consequence: STIM1 NM_001382567.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-3855664-A-G is Benign according to our data. Variant chr11-3855664-A-G is described in ClinVar as [Benign]. Clinvar id is 1289827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1	c.-607A>G		5_prime_UTR_variant	1/13	ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2	c.-607A>G		5_prime_UTR_variant	1/13	5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 68749 AN: 144728 Hom.: 16162 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.435

GnomAD4 exome AF: 0.508 AC: 66 AN: 130 Hom.: 20 Cov.: 0 AF XY: 0.500 AC XY: 37 AN XY: 74

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.487

Gnomad4 NFE exome AF: 0.542

GnomAD4 genome AF: 0.475 AC: 68771 AN: 144780 Hom.: 16166 Cov.: 33 AF XY: 0.479 AC XY: 33753 AN XY: 70458

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.437

Alfa AF: 0.474 Hom.: 2062

Bravo AF: 0.471

Asia WGS AF: 0.515 AC: 1744 AN: 3388

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

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	14
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11828037; hg19: chr11-3876894;