11-3855883-CTCTCTTCTCT-CTCTCTTCTCTTCTCT

Variant names:

• chr11-3855883-C-CTCTCT
• rs3061890
• NM_001382567.1:c.-370_-366dupTCTTC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001382567.1(STIM1):​c.-370_-366dupTCTTC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: STIM1 NM_001382567.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• 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]

MIR4687 (HGNC:41712): (microRNA 4687) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000316 (48/151792) while in subpopulation AFR AF = 0.00065 (27/41518). AF 95% confidence interval is 0.000459. There are 0 homozygotes in GnomAd4. There are 21 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	NM_001382567.1	MANE Select	c.-370_-366dupTCTTC		5_prime_UTR	Exon 1 of 13	NP_001369496.1	H0YDB2
	STIM1	NM_001277961.3		c.-370_-366dupTCTTC		5_prime_UTR	Exon 1 of 12	NP_001264890.1	G0XQ39
	STIM1	NM_001382568.1		c.-370_-366dupTCTTC		5_prime_UTR	Exon 1 of 12	NP_001369497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	ENST00000526596.2	TSL:5 MANE Select	c.-370_-366dupTCTTC		5_prime_UTR	Exon 1 of 13	ENSP00000433266.2	H0YDB2
	STIM1	ENST00000616714.4	TSL:1	c.-370_-366dupTCTTC		5_prime_UTR	Exon 1 of 12	ENSP00000478059.1	G0XQ39
	STIM1	ENST00000300737.8	TSL:1	c.-370_-366dupTCTTC		5_prime_UTR	Exon 1 of 12	ENSP00000300737.4	Q13586-1

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 151672 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000186 AC: 16 AN: 86120 Hom.: 0 Cov.: 0 AF XY: 0.000169 AC XY: 8 AN XY: 47246

African (AFR) AF: 0.000816 AC: 2 AN: 2450

American (AMR) AF: 0.000430 AC: 2 AN: 4650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1834

East Asian (EAS) AF: 0.000512 AC: 2 AN: 3910

South Asian (SAS) AF: 0.000179 AC: 3 AN: 16734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000104 AC: 5 AN: 48146

Other (OTH) AF: 0.000462 AC: 2 AN: 4332

GnomAD4 genome AF: 0.000316 AC: 48 AN: 151792 Hom.: 0 Cov.: 0 AF XY: 0.000283 AC XY: 21 AN XY: 74176

African (AFR) AF: 0.000650 AC: 27 AN: 41518

American (AMR) AF: 0.000131 AC: 2 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5088

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67802

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76

Splicing

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

Other links and lift over

dbSNP: rs3061890; hg19: chr11-3877113;