11-3888056-G-A

Variant names:

• chr11-3888056-G-A
• rs1869084
• NM_001382567.1:c.139+31647G>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.139+31647G>A variant causes a intron change. The variant allele was found at a frequency of 0.257 in 151,594 control chromosomes in the GnomAD database, including 5,703 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 0.26 (5700 hom., cov: 29)
  • Exomes 𝑓: 0.30 (3 hom.)
• Consequence: STIM1 NM_001382567.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 4 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)

ENSG00000300446 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 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.139+31647G>A		intron	N/A	NP_001369496.1
	STIM1	NM_001277961.3		c.139+31647G>A		intron	N/A	NP_001264890.1
	STIM1	NM_001382566.1		c.-84+32640G>A		intron	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.139+31647G>A		intron	N/A	ENSP00000433266.2
	STIM1	ENST00000616714.4	TSL:1	c.139+31647G>A		intron	N/A	ENSP00000478059.1
	STIM1	ENST00000300737.8	TSL:1	c.139+31647G>A		intron	N/A	ENSP00000300737.4

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38958 AN: 151398 Hom.: 5699 Cov.: 29

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.302 AC: 26 AN: 86 Hom.: 3 Cov.: 0 AF XY: 0.333 AC XY: 20 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 2

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: 0.500 AC: 3 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.300 AC: 21 AN: 70

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.257 AC: 38964 AN: 151508 Hom.: 5700 Cov.: 29 AF XY: 0.263 AC XY: 19448 AN XY: 73956

African (AFR) AF: 0.127 AC: 5263 AN: 41330

American (AMR) AF: 0.250 AC: 3807 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 969 AN: 3466

East Asian (EAS) AF: 0.261 AC: 1337 AN: 5128

South Asian (SAS) AF: 0.407 AC: 1948 AN: 4788

European-Finnish (FIN) AF: 0.392 AC: 4073 AN: 10378

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.306 AC: 20757 AN: 67918

Other (OTH) AF: 0.268 AC: 563 AN: 2100

Alfa AF: 0.294 Hom.: 11381

Bravo AF: 0.237

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.78
PhyloP100		4.1
PromoterAI		-0.00040	Neutral
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: rs1869084; hg19: chr11-3909286;