dbSNP rs7801498: ORAI2:c.*2096G>A (chr7-102449148-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

12 publications found

Variant links:

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]

ORAI2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001126340.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126340.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ORAI2	NM_001126340.3	MANE Select	c.*2096G>A	3_prime_UTR	Exon 4 of 4	NP_001119812.1	Q96SN7
ORAI2	NM_001271818.2		c.*2096G>A	3_prime_UTR	Exon 4 of 4	NP_001258747.1	Q96SN7
ORAI2	NM_032831.4		c.*2096G>A	3_prime_UTR	Exon 3 of 3	NP_116220.1	Q96SN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ORAI2	ENST00000495936.7	TSL:2 MANE Select	c.*2096G>A	3_prime_UTR	Exon 4 of 4	ENSP00000420178.2	Q96SN7
ORAI2	ENST00000473939.2	TSL:1	c.*2096G>A	3_prime_UTR	Exon 3 of 3	ENSP00000417928.1	Q96SN7
ORAI2	ENST00000498661.6	TSL:1	c.*2096G>A	3_prime_UTR	Exon 3 of 3	ENSP00000418464.2	Q96SN7

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83484

AN:

151876

Hom.:

24280

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.773

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.549

AC:

83493

AN:

151996

Hom.:

24272

Cov.:

AF XY:

0.543

AC XY:

40349

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.359

AC:

14888

AN:

41474

American (AMR)

AF:

0.583

AC:

8889

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

2543

AN:

3472

East Asian (EAS)

AF:

0.390

AC:

2012

AN:

5164

South Asian (SAS)

AF:

0.501

AC:

2415

AN:

4820

European-Finnish (FIN)

AF:

0.577

AC:

6091

AN:

10558

Middle Eastern (MID)

AF:

0.735

AC:

216

AN:

294

European-Non Finnish (NFE)

AF:

0.658

AC:

44719

AN:

67954

Other (OTH)

AF:

0.589

AC:

1242

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1816

3633

5449

7266

9082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.618

Hom.:

54829

Bravo

AF:

0.548

Asia WGS

AF:

0.429

AC:

1494

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.7

(source)

DANN

Benign

0.54

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over