rs720571

Positions:

• chr11-3980098-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.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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM1	NM_001382567.1	c.270+12416G>T		intron_variant		ENST00000526596.2	NP_001369496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM1	ENST00000526596.2	c.270+12416G>T		intron_variant		5	NM_001382567.1	ENSP00000433266.2

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

Gnomad4 AFR AF: 0.0681

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.250

Alfa AF: 0.294 Hom.: 918

Bravo AF: 0.220

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.74

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: rs720571; hg19: chr11-4001328;