rs1561876

chr11-4092165-G-Achr11-4092165-G-Cchr11-4092165-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.*367G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 334,640 control chromosomes in the GnomAD database, including 111,378 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 0.73 (43553 hom., cov: 31)
  • Exomes 𝑓: 0.86 (67825 hom.)
• Consequence: STIM1 NM_001382567.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1	c.*367G>A		3_prime_UTR_variant	13/13	ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2	c.*367G>A		3_prime_UTR_variant	13/13	5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110271 AN: 151882 Hom.: 43557 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.855 AC: 156188 AN: 182640 Hom.: 67825 Cov.: 0 AF XY: 0.862 AC XY: 84163 AN XY: 97614

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.910

Gnomad4 FIN exome AF: 0.871

Gnomad4 NFE exome AF: 0.884

Gnomad4 OTH exome AF: 0.839

GnomAD4 genome AF: 0.726 AC: 110289 AN: 152000 Hom.: 43553 Cov.: 31 AF XY: 0.728 AC XY: 54072 AN XY: 74294

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.771

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.910

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.755

Alfa AF: 0.815 Hom.: 21928

Bravo AF: 0.698

Asia WGS AF: 0.754 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.1
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1561876; hg19: chr11-4113395;