4-26942692-C-T

Position:

• chr4-26942692-C-T

Variant summary

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

The ENST00000467087.7(STIM2):​c.283-14920C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,032 control chromosomes in the GnomAD database, including 2,631 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 0.18 (2631 hom., cov: 32)
• Consequence: STIM2 ENST00000467087.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIM2	NM_020860.4	c.283-14920C>T		intron_variant		ENST00000467087.7	NP_065911.3
STIM2	NM_001169117.2	c.283-14920C>T		intron_variant			NP_001162588.1
STIM2	NM_001169118.2	c.283-14920C>T		intron_variant			NP_001162589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIM2	ENST00000467087.7	c.283-14920C>T		intron_variant		1	NM_020860.4	ENSP00000419073	P2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27010 AN: 151914 Hom.: 2627 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.178 AC: 27031 AN: 152032 Hom.: 2631 Cov.: 32 AF XY: 0.181 AC XY: 13439 AN XY: 74296

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.191

Alfa AF: 0.180 Hom.: 3557

Bravo AF: 0.177

Asia WGS AF: 0.340 AC: 1180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.18

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: rs6844153; hg19: chr4-26944314;