chr7-102449148-G-A

Position:

• chr7-102449148-G-A

Variant summary

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

The NM_001126340.3(ORAI2):​c.*2096G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,026 control chromosomes in the GnomAD database, including 24,281 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 0.55 (24272 hom., cov: 32)
  • Exomes 𝑓: 0.70 (9 hom.)
• Consequence: ORAI2 NM_001126340.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

ORAI2 (HGNC:21667): (ORAI calcium release-activated calcium modulator 2) Predicted to enable store-operated calcium channel activity. Predicted to be involved in store-operated calcium entry. Predicted to be located in growth cone. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORAI2	NM_001126340.3	c.*2096G>A		3_prime_UTR_variant	4/4	ENST00000495936.7
ORAI2	NM_001271818.2	c.*2096G>A		3_prime_UTR_variant	4/4
ORAI2	NM_001271819.2	c.*2096G>A		3_prime_UTR_variant	3/3
ORAI2	NM_032831.4	c.*2096G>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORAI2	ENST00000495936.7	c.*2096G>A		3_prime_UTR_variant	4/4	2	NM_001126340.3	P1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83484 AN: 151876 Hom.: 24280 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.700 AC: 21 AN: 30 Hom.: 9 Cov.: 0 AF XY: 0.773 AC XY: 17 AN XY: 22

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.549 AC: 83493 AN: 151996 Hom.: 24272 Cov.: 32 AF XY: 0.543 AC XY: 40349 AN XY: 74284

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.589

Alfa AF: 0.629 Hom.: 10126

Bravo AF: 0.548

Asia WGS AF: 0.429 AC: 1494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.54

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: rs7801498; hg19: chr7-102089595;