Variant 12-3638118-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001144958.2(CRACR2A):c.1602+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00388 in 1,538,484 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 18 hom. )

Consequence

CRACR2A
NM_001144958.2 splice_donor_region, intron

Scores

Splicing: ADA: 0.002503

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.405

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 12-3638118-C-T is Benign according to our data. Variant chr12-3638118-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642578.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACR2A	NM_001144958.2 linkuse as main transcript	c.1602+6G>A		splice_donor_region_variant, intron_variant		ENST00000440314.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000440314.7 linkuse as main transcript	c.1602+6G>A		splice_donor_region_variant, intron_variant		2	NM_001144958.2	P1	Q9BSW2-2
CRACR2A	ENST00000333750.9 linkuse as main transcript	c.*599+6G>A		splice_donor_region_variant, intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00270

AC:

411

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00384

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00273

AC:

399

AN:

146216

Hom.:

AF XY:

0.00269

AC XY:

211

AN XY:

78356

show subpopulations

Gnomad AFR exome

AF:

0.000565

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.000250

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000270

Gnomad FIN exome

AF:

0.00379

Gnomad NFE exome

AF:

0.00465

Gnomad OTH exome

AF:

0.00288

GnomAD4 exome

AF:

0.00401

AC:

5560

AN:

1386210

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

2677

AN XY:

681280

show subpopulations

Gnomad4 AFR exome

AF:

0.000672

Gnomad4 AMR exome

AF:

0.00261

Gnomad4 ASJ exome

AF:

0.000525

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000229

Gnomad4 FIN exome

AF:

0.00444

Gnomad4 NFE exome

AF:

0.00461

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

AF:

0.00270

AC:

411

AN:

152274

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00384

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00256

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

CRACR2A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

Cadd

Benign

6.2

Dann

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0025

dbscSNV1_RF

Benign

0.062

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