Variant 11-3855664-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382567.1(STIM1):c.-607A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 144,910 control chromosomes in the GnomAD database, including 16,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 16166 hom., cov: 33)

Exomes 𝑓: 0.51 ( 20 hom. )

Consequence

STIM1
NM_001382567.1 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0370

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-3855664-A-G is Benign according to our data. Variant chr11-3855664-A-G is described in ClinVar as [Benign]. Clinvar id is 1289827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM1	NM_001382567.1 linkuse as main transcript	c.-607A>G		5_prime_UTR_variant	1/13	ENST00000526596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM1	ENST00000526596.2 linkuse as main transcript	c.-607A>G		5_prime_UTR_variant	1/13	5	NM_001382567.1	P3

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

68749

AN:

144728

Hom.:

16162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.435

GnomAD4 exome

AF:

0.508

AC:

AN:

130

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.487

Gnomad4 NFE exome

AF:

0.542

GnomAD4 genome

AF:

0.475

AC:

68771

AN:

144780

Hom.:

16166

Cov.:

AF XY:

0.479

AC XY:

33753

AN XY:

70458

show subpopulations

Gnomad4 AFR

AF:

0.455

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.550

Gnomad4 SAS

AF:

0.558

Gnomad4 FIN

AF:

0.498

Gnomad4 NFE

AF:

0.480

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.474

Hom.:

2062

Bravo

AF:

0.471

Asia WGS

AF:

0.515

AC:

1744

AN:

3388

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.50

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over