rs12505133

Positions:

• chr4-26882287-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020860.4(STIM2):​c.151+20918T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,082 control chromosomes in the GnomAD database, including 3,159 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 0.20 (3159 hom., cov: 32)
• Consequence: STIM2 NM_020860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

STIM2 (HGNC:19205): (stromal interaction molecule 2) This gene is a member of the stromal interaction molecule (STIM) family and likely arose, along with related family member STIM1, from a common ancestral gene. The encoded protein functions to regulate calcium concentrations in the cytosol and endoplasmic reticulum, and is involved in the activation of plasma membrane Orai Ca(2+) entry channels. This gene initiates translation from a non-AUG (UUG) start site. A signal peptide is cleaved from the resulting protein. Multiple transcript variants result from alternative splicing. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIM2	NM_020860.4	c.151+20918T>C		intron_variant		ENST00000467087.7
STIM2	NM_001169117.2	c.151+20918T>C		intron_variant
STIM2	NM_001169118.2	c.151+20918T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIM2	ENST00000467087.7	c.151+20918T>C		intron_variant		1	NM_020860.4	P2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30287 AN: 151964 Hom.: 3155 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30316 AN: 152082 Hom.: 3159 Cov.: 32 AF XY: 0.200 AC XY: 14839 AN XY: 74360

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.183

Alfa AF: 0.215 Hom.: 1965

Bravo AF: 0.199

Asia WGS AF: 0.150 AC: 523 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.73

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: rs12505133; hg19: chr4-26883909;