rs242033

chr12-3676907-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144958.2(CRACR2A):c.524+2008T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,978 control chromosomes in the GnomAD database, including 10,693 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 0.37 (10693 hom., cov: 32)
• Consequence: CRACR2A NM_001144958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACR2A	NM_001144958.2	c.524+2008T>G		intron_variant		ENST00000440314.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000440314.7	c.524+2008T>G		intron_variant		2	NM_001144958.2	P1
CRACR2A	ENST00000252322.1	c.524+2008T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55923 AN: 151862 Hom.: 10676 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 55994 AN: 151978 Hom.: 10693 Cov.: 32 AF XY: 0.366 AC XY: 27202 AN XY: 74310

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.380

Alfa AF: 0.343 Hom.: 17299

Bravo AF: 0.375

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.3
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs242033; hg19: chr12-3786073;