rs6833149

Positions:

• chr4-27009920-T-A
• chr4-27009920-T-G

Variant summary

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

The NM_020860.4(STIM2):​c.1489+918T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,148 control chromosomes in the GnomAD database, including 7,757 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 0.32 (7757 hom., cov: 33)
• Consequence: STIM2 NM_020860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM2	NM_020860.4	c.1489+918T>A		intron_variant		ENST00000467087.7	NP_065911.3
STIM2	NM_001169117.2	c.1489+918T>A		intron_variant			NP_001162588.1
STIM2	NM_001169118.2	c.1513+918T>A		intron_variant			NP_001162589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM2	ENST00000467087.7	c.1489+918T>A		intron_variant		1	NM_020860.4	ENSP00000419073	P2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48294 AN: 152030 Hom.: 7758 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.318 AC: 48329 AN: 152148 Hom.: 7757 Cov.: 33 AF XY: 0.320 AC XY: 23808 AN XY: 74370

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.298

Alfa AF: 0.306 Hom.: 919

Bravo AF: 0.317

Asia WGS AF: 0.334 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.72

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: rs6833149; hg19: chr4-27011542;