11-3855605-G-GCC

Position:

• chr11-3855605-G-GCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001382566.1(STIM1):​c.-84+190_-84+191insCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 139,206 control chromosomes in the GnomAD database, including 69,521 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (69521 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: STIM1 NM_001382566.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260

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 -10 ACMG points.

• BP6: Variant 11-3855605-G-GCC is Benign according to our data. Variant chr11-3855605-G-GCC is described in ClinVar as [Benign]. Clinvar id is 1234253.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM1	NM_001382566.1	c.-84+190_-84+191insCC		intron_variant			NP_001369495.1
STIM1	NM_001382575.1	c.-84+870_-84+871insCC		intron_variant			NP_001369504.1
STIM1	NM_001382576.1	c.-84+952_-84+953insCC		intron_variant			NP_001369505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM1	ENST00000698911.1	c.-84+190_-84+191insCC		intron_variant				ENSP00000514025.1
STIM1	ENST00000698913.1	c.-84+190_-84+191insCC		intron_variant				ENSP00000514027.1
STIM1	ENST00000698910.1	c.-220+870_-220+871insCC		intron_variant				ENSP00000514024.1

Frequencies

GnomAD3 genomes AF: 0.999 AC: 139066 AN: 139172 Hom.: 69502 Cov.: 32

Gnomad AFR AF: 0.999

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.999 AC: 139102 AN: 139206 Hom.: 69521 Cov.: 32 AF XY: 0.999 AC XY: 67370 AN XY: 67424

Gnomad4 AFR AF: 0.999

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 1.00

Alfa AF: 0.00160 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs575153378; hg19: chr11-3876835;