rs720571

Variant names:

• chr11-3980098-G-T
• rs720571
• NM_001382567.1:c.270+12416G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382567.1(STIM1):​c.270+12416G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,912 control chromosomes in the GnomAD database, including 5,658 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 0.24 (5658 hom., cov: 31)
• Consequence: STIM1 NM_001382567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
• Stormorken syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, PanelApp Australia
• tubular aggregate myopathy

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	NM_001382567.1	MANE Select	c.270+12416G>T		intron	N/A	NP_001369496.1	H0YDB2
	STIM1	NM_001277961.3		c.270+12416G>T		intron	N/A	NP_001264890.1	G0XQ39
	STIM1	NM_001382566.1		c.48+12416G>T		intron	N/A	NP_001369495.1	A0A8V8TNW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	ENST00000526596.2	TSL:5 MANE Select	c.270+12416G>T		intron	N/A	ENSP00000433266.2	H0YDB2
	STIM1	ENST00000616714.4	TSL:1	c.270+12416G>T		intron	N/A	ENSP00000478059.1	G0XQ39
	STIM1	ENST00000300737.8	TSL:1	c.270+12416G>T		intron	N/A	ENSP00000300737.4	Q13586-1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37197 AN: 151794 Hom.: 5655 Cov.: 31

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.254

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37206 AN: 151912 Hom.: 5658 Cov.: 31 AF XY: 0.252 AC XY: 18670 AN XY: 74218

African (AFR) AF: 0.0681 AC: 2822 AN: 41442

American (AMR) AF: 0.253 AC: 3856 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3462

East Asian (EAS) AF: 0.289 AC: 1495 AN: 5176

South Asian (SAS) AF: 0.450 AC: 2170 AN: 4820

European-Finnish (FIN) AF: 0.370 AC: 3889 AN: 10518

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21203 AN: 67922

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.286 Hom.: 922

Bravo AF: 0.220

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.74
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs720571; hg19: chr11-4001328;