rs242033

Variant names:

• chr12-3676907-A-C
• rs242033
• NM_001144958.2:c.524+2008T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2A	NM_001144958.2	MANE Select	c.524+2008T>G		intron	N/A	NP_001138430.1	Q9BSW2-2
	CRACR2A	NM_032680.4		c.524+2008T>G		intron	N/A	NP_116069.1	Q9BSW2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2A	ENST00000440314.7	TSL:2 MANE Select	c.524+2008T>G		intron	N/A	ENSP00000409382.2	Q9BSW2-2
	CRACR2A	ENST00000252322.1	TSL:1	c.524+2008T>G		intron	N/A	ENSP00000252322.1	Q9BSW2-1
	CRACR2A	ENST00000893446.1		c.524+2008T>G		intron	N/A	ENSP00000563505.1

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

African (AFR) AF: 0.458 AC: 18979 AN: 41408

American (AMR) AF: 0.307 AC: 4687 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2445 AN: 5158

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4822

European-Finnish (FIN) AF: 0.262 AC: 2768 AN: 10576

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22810 AN: 67950

Other (OTH) AF: 0.380 AC: 802 AN: 2110

Alfa AF: 0.349 Hom.: 26276

Bravo AF: 0.375

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.56
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs242033; hg19: chr12-3786073;