rs1465952

Variant names:

• chr11-4093309-G-A
• rs1465952
• NM_001382567.1:c.*1511G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-4093309-G-A
• chr11-4093309-G-C
• chr11-4093309-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382567.1(STIM1):​c.*1511G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,144 control chromosomes in the GnomAD database, including 51,871 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (51871 hom., cov: 32)
  • Exomes 𝑓: 0.94 (150 hom.)
  • Failed GnomAD Quality Control
• Consequence: STIM1 NM_001382567.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIM1	NM_001382567.1	c.*1511G>A		downstream_gene_variant		ENST00000526596.2	NP_001369496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIM1	ENST00000526596.2	c.*1511G>A		downstream_gene_variant		5	NM_001382567.1	ENSP00000433266.2

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123117 AN: 152026 Hom.: 51851 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.934

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.839

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.936 AC: 322 AN: 344 Hom.: 150 AF XY: 0.951 AC XY: 196 AN XY: 206

Gnomad4 FIN exome AF: 0.935

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.810 AC: 123177 AN: 152144 Hom.: 51871 Cov.: 32 AF XY: 0.813 AC XY: 60509 AN XY: 74388

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.935

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.838

Alfa AF: 0.893 Hom.: 65511

Bravo AF: 0.793

Asia WGS AF: 0.917 AC: 3188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1465952; hg19: chr11-4114539;