chr11-4092165-G-A

Variant names:

• chr11-4092165-G-A
• rs1561876
• NM_001382567.1:c.*367G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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]

STIM1 Gene-Disease associations (from GenCC):

• myopathy, tubular aggregate, 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Stormorken syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• tubular aggregate myopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• combined immunodeficiency due to STIM1 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	NM_001382567.1	MANE Select	c.*367G>A		3_prime_UTR	Exon 13 of 13	NP_001369496.1
	STIM1	NR_168436.1		n.2349G>A		non_coding_transcript_exon	Exon 8 of 8
	STIM1	NR_168437.1		n.2854G>A		non_coding_transcript_exon	Exon 11 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIM1	ENST00000526596.2	TSL:5 MANE Select	c.*367G>A		3_prime_UTR	Exon 13 of 13	ENSP00000433266.2
	STIM1	ENST00000616714.4	TSL:1	c.*367G>A		3_prime_UTR	Exon 12 of 12	ENSP00000478059.1
	STIM1	ENST00000300737.8	TSL:1	c.*367G>A		3_prime_UTR	Exon 12 of 12	ENSP00000300737.4

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

African (AFR) AF: 0.363 AC: 2155 AN: 5932

American (AMR) AF: 0.774 AC: 7304 AN: 9442

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 4008 AN: 4816

East Asian (EAS) AF: 0.759 AC: 6751 AN: 8894

South Asian (SAS) AF: 0.910 AC: 27588 AN: 30320

European-Finnish (FIN) AF: 0.871 AC: 6226 AN: 7150

Middle Eastern (MID) AF: 0.848 AC: 575 AN: 678

European-Non Finnish (NFE) AF: 0.884 AC: 93519 AN: 105800

Other (OTH) AF: 0.839 AC: 8062 AN: 9608

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

African (AFR) AF: 0.383 AC: 15866 AN: 41418

American (AMR) AF: 0.771 AC: 11783 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2849 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3898 AN: 5154

South Asian (SAS) AF: 0.910 AC: 4381 AN: 4814

European-Finnish (FIN) AF: 0.850 AC: 8983 AN: 10570

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 59998 AN: 67984

Other (OTH) AF: 0.755 AC: 1589 AN: 2106

Alfa AF: 0.809 Hom.: 110189

Bravo AF: 0.698

Asia WGS AF: 0.754 AC: 2623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.1
DANN	Benign	0.79
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1561876; hg19: chr11-4113395;