Variant 12-3627579-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001144958.2(CRACR2A):c.1818-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,551,200 control chromosomes in the GnomAD database, including 327,628 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 35887 hom., cov: 32)

Exomes 𝑓: 0.64 ( 291741 hom. )

Consequence

CRACR2A
NM_001144958.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.22

Variant links:

Genes affected

CRACR2A (HGNC:28657): (calcium release activated channel regulator 2A) Enables GTPase activity and calcium ion binding activity. Involved in several processes, including activation of store-operated calcium channel activity; positive regulation of JNK cascade; and store-operated calcium entry. Located in several cellular components, including Golgi apparatus; Weibel-Palade body; and immunological synapse. [provided by Alliance of Genome Resources, Apr 2022]

CRACR2A 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=-0.86).

BP6

Variant 12-3627579-T-C is Benign according to our data. Variant chr12-3627579-T-C is described in ClinVar as [Benign]. Clinvar id is 2688307.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACR2A	NM_001144958.2 linkuse as main transcript	c.1818-29A>G		intron_variant		ENST00000440314.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000440314.7 linkuse as main transcript	c.1818-29A>G		intron_variant		2	NM_001144958.2	P1	Q9BSW2-2
CRACR2A	ENST00000333750.9 linkuse as main transcript	c.*815-29A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.684

AC:

103988

AN:

151962

Hom.:

35837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.691

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.643

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.637

Gnomad OTH

AF:

0.716

GnomAD3 exomes

AF:

0.669

AC:

104731

AN:

156530

Hom.:

35382

AF XY:

0.666

AC XY:

55188

AN XY:

82914

show subpopulations

Gnomad AFR exome

AF:

0.780

Gnomad AMR exome

AF:

0.755

Gnomad ASJ exome

AF:

0.690

Gnomad EAS exome

AF:

0.609

Gnomad SAS exome

AF:

0.658

Gnomad FIN exome

AF:

0.641

Gnomad NFE exome

AF:

0.640

Gnomad OTH exome

AF:

0.666

GnomAD4 exome

AF:

0.645

AC:

901878

AN:

1399120

Hom.:

291741

Cov.:

AF XY:

0.645

AC XY:

445279

AN XY:

690094

show subpopulations

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.756

Gnomad4 ASJ exome

AF:

0.681

Gnomad4 EAS exome

AF:

0.591

Gnomad4 SAS exome

AF:

0.661

Gnomad4 FIN exome

AF:

0.640

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.656

GnomAD4 genome

AF:

0.685

AC:

104099

AN:

152080

Hom.:

35887

Cov.:

AF XY:

0.686

AC XY:

50964

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.773

Gnomad4 AMR

AF:

0.727

Gnomad4 ASJ

AF:

0.691

Gnomad4 EAS

AF:

0.606

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.637

Gnomad4 OTH

AF:

0.718

Alfa

AF:

0.664

Hom.:

6178

Bravo

AF:

0.698

Asia WGS

AF:

0.646

AC:

2248

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 96% of patients studied by a panel of primary immunodeficiencies. Number of patients: 91. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

Cadd

Benign

0.0040

Dann

Benign

0.28

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

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