Variant 12-121626524-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000698901.1(ORAI1):n.16C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 169,778 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 38 hom., cov: 30)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

ORAI1
ENST00000698901.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.201

Variant links:

Genes affected

ORAI1 (HGNC:):

ORAI1 links:

ORAI1 (HGNC:25896): (ORAI calcium release-activated calcium modulator 1) The protein encoded by this gene is a membrane calcium channel subunit that is activated by the calcium sensor STIM1 when calcium stores are depleted. This type of channel is the primary way for calcium influx into T-cells. Defects in this gene are a cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 1 (IDTICED1). [provided by RefSeq, Sep 2011]

ORAI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 12-121626524-C-A is Benign according to our data. Variant chr12-121626524-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1205576.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1815/151942) while in subpopulation AFR AF= 0.0418 (1735/41498). AF 95% confidence interval is 0.0402. There are 38 homozygotes in gnomad4. There are 835 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
	use as main transcript	n.121626524C>A		intergenic_region
ORAI1	NR_186857.1 linkuse as main transcript	n.-6C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
ORAI1	ENST00000698901.1 linkuse as main transcript	n.16C>A	non_coding_transcript_exon_variant	1/2
ORAI1	ENST00000617316.2 linkuse as main transcript	c.-219C>A	upstream_gene_variant		1	ENSP00000482568.2	Q96D31-1
ORAI1	ENST00000646827.1 linkuse as main transcript	n.-26C>A	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1813

AN:

151836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0419

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00672

GnomAD4 exome

AF:

0.00123

AC:

AN:

17836

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

9988

show subpopulations

Gnomad4 AFR exome

AF:

0.0497

Gnomad4 AMR exome

AF:

0.00162

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000797

Gnomad4 OTH exome

AF:

0.00190

GnomAD4 genome

AF:

0.0119

AC:

1815

AN:

151942

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

835

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0418

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.000425

Hom.:

Bravo

AF:

0.0138

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over