rs1869084

Positions:

• chr11-3888056-G-A
• chr11-3888056-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.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

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=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM1	NM_001382567.1	c.139+31647G>A		intron_variant		ENST00000526596.2	NP_001369496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM1	ENST00000526596.2	c.139+31647G>A		intron_variant		5	NM_001382567.1	ENSP00000433266	P3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.268

Alfa AF: 0.301 Hom.: 9260

Bravo AF: 0.237

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1869084; hg19: chr11-3909286;