Variant 12-3627568-C-T 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.1818-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,551,238 control chromosomes in the GnomAD database, including 56,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 7866 hom., cov: 32)

Exomes 𝑓: 0.26 ( 48195 hom. )

Consequence

CRACR2A
NM_001144958.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.49

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=-0.88).

BP6

Variant 12-3627568-C-T is Benign according to our data. Variant chr12-3627568-C-T is described in ClinVar as [Benign]. Clinvar id is 2688078.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 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.1818-18G>A		intron_variant		ENST00000440314.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000440314.7 linkuse as main transcript	c.1818-18G>A		intron_variant		2	NM_001144958.2	P1	Q9BSW2-2
CRACR2A	ENST00000333750.9 linkuse as main transcript	c.*815-18G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47081

AN:

151978

Hom.:

7863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.421

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.284

AC:

44453

AN:

156600

Hom.:

6861

AF XY:

0.275

AC XY:

22822

AN XY:

82920

show subpopulations

Gnomad AFR exome

AF:

0.436

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.410

Gnomad SAS exome

AF:

0.203

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.258

AC:

360657

AN:

1399142

Hom.:

48195

Cov.:

AF XY:

0.255

AC XY:

176294

AN XY:

690086

show subpopulations

Gnomad4 AFR exome

AF:

0.423

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.376

Gnomad4 SAS exome

AF:

0.207

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.310

AC:

47116

AN:

152096

Hom.:

7866

Cov.:

AF XY:

0.315

AC XY:

23435

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.421

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.402

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.307

Alfa

AF:

0.277

Hom.:

1265

Bravo

AF:

0.318

Asia WGS

AF:

0.309

AC:

1074

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 58% of patients studied by a panel of primary immunodeficiencies. Number of patients: 55. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.19

Dann

Benign

0.78

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