chr4-26913215-A-G

Variant names:

• chr4-26913215-A-G
• rs11727649
• NM_020860.4:c.152-6289A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020860.4(STIM2):​c.152-6289A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,126 control chromosomes in the GnomAD database, including 2,823 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 (2823 hom., cov: 32)
• Consequence: STIM2 NM_020860.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIM2	NM_020860.4	c.152-6289A>G		intron_variant	Intron 1 of 11	ENST00000467087.7	NP_065911.3
STIM2	NM_001169118.2	c.152-6289A>G		intron_variant	Intron 1 of 12		NP_001162589.1
STIM2	NM_001169117.2	c.152-6289A>G		intron_variant	Intron 1 of 12		NP_001162588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIM2	ENST00000467087.7	c.152-6289A>G		intron_variant	Intron 1 of 11	1	NM_020860.4	ENSP00000419073.2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27871 AN: 152010 Hom.: 2820 Cov.: 32

Gnomad AFR AF: 0.0976

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.183 AC: 27886 AN: 152126 Hom.: 2823 Cov.: 32 AF XY: 0.184 AC XY: 13662 AN XY: 74372

African (AFR) AF: 0.0976 AC: 4051 AN: 41510

American (AMR) AF: 0.245 AC: 3746 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1187 AN: 5194

South Asian (SAS) AF: 0.143 AC: 689 AN: 4818

European-Finnish (FIN) AF: 0.203 AC: 2139 AN: 10558

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.220 AC: 14977 AN: 67994

Other (OTH) AF: 0.173 AC: 366 AN: 2114

Alfa AF: 0.206 Hom.: 1719

Bravo AF: 0.182

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.80
PhyloP100		0.20
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: rs11727649; hg19: chr4-26914837;