chr11-4093309-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

STIM1 Gene-Disease associations (from GenCC):

• myopathy, tubular aggregate, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Stormorken syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• tubular aggregate myopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• combined immunodeficiency due to STIM1 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382567.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	NM_001382567.1	MANE Select	c.*1511G>A		downstream_gene	N/A	NP_001369496.1
	STIM1	NM_001277961.3		c.*1511G>A		downstream_gene	N/A	NP_001264890.1
	STIM1	NM_001382566.1		c.*1511G>A		downstream_gene	N/A	NP_001369495.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	ENST00000526596.2	TSL:5 MANE Select	c.*1511G>A		downstream_gene	N/A	ENSP00000433266.2
	STIM1	ENST00000616714.4	TSL:1	c.*1511G>A		downstream_gene	N/A	ENSP00000478059.1
	STIM1	ENST00000300737.8	TSL:1	c.*1511G>A		downstream_gene	N/A	ENSP00000300737.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.935 AC: 318 AN: 340

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.546 AC: 22654 AN: 41458

American (AMR) AF: 0.889 AC: 13602 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3007 AN: 3468

East Asian (EAS) AF: 0.946 AC: 4895 AN: 5174

South Asian (SAS) AF: 0.935 AC: 4502 AN: 4816

European-Finnish (FIN) AF: 0.916 AC: 9701 AN: 10594

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61987 AN: 68024

Other (OTH) AF: 0.838 AC: 1761 AN: 2102

Alfa AF: 0.878 Hom.: 163547

Bravo AF: 0.793

Asia WGS AF: 0.917 AC: 3188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.4
DANN	Benign	0.74
PhyloP100		0.30
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1465952; hg19: chr11-4114539;