12-3648382-T-C

Variant names:

• chr12-3648382-T-C
• rs887304
• ENST00000252322.1:c.*90A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000252322.1(CRACR2A):​c.*90A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 1,522,590 control chromosomes in the GnomAD database, including 410,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45899 hom., cov: 31)
  • Exomes 𝑓: 0.73 (364693 hom.)
• Consequence: CRACR2A ENST00000252322.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710
• Publications: 26 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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 12-3648382-T-C is Benign according to our data. Variant chr12-3648382-T-C is described in ClinVar as Benign. ClinVar VariationId is 2687954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252322.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2A	NM_001144958.2	MANE Select	c.1118+160A>G		intron	N/A	NP_001138430.1
	CRACR2A	NM_032680.4		c.*90A>G		3_prime_UTR	Exon 11 of 11	NP_116069.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2A	ENST00000252322.1	TSL:1	c.*90A>G		3_prime_UTR	Exon 11 of 11	ENSP00000252322.1
	CRACR2A	ENST00000440314.7	TSL:2 MANE Select	c.1118+160A>G		intron	N/A	ENSP00000409382.2
	CRACR2A	ENST00000333750.9	TSL:2	n.*90A>G		non_coding_transcript_exon	Exon 5 of 15	ENSP00000331047.5

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117179 AN: 151898 Hom.: 45851 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.726 AC: 994809 AN: 1370574 Hom.: 364693 Cov.: 56 AF XY: 0.728 AC XY: 489889 AN XY: 672850

African (AFR) AF: 0.877 AC: 27277 AN: 31104

American (AMR) AF: 0.868 AC: 30253 AN: 34834

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 16016 AN: 21060

East Asian (EAS) AF: 0.994 AC: 38543 AN: 38764

South Asian (SAS) AF: 0.833 AC: 62221 AN: 74728

European-Finnish (FIN) AF: 0.649 AC: 27021 AN: 41662

Middle Eastern (MID) AF: 0.806 AC: 3886 AN: 4822

European-Non Finnish (NFE) AF: 0.700 AC: 747262 AN: 1067142

Other (OTH) AF: 0.750 AC: 42330 AN: 56458

GnomAD4 genome AF: 0.772 AC: 117286 AN: 152016 Hom.: 45899 Cov.: 31 AF XY: 0.775 AC XY: 57555 AN XY: 74278

African (AFR) AF: 0.869 AC: 36045 AN: 41498

American (AMR) AF: 0.829 AC: 12678 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2608 AN: 3466

East Asian (EAS) AF: 0.991 AC: 5092 AN: 5138

South Asian (SAS) AF: 0.842 AC: 4051 AN: 4810

European-Finnish (FIN) AF: 0.651 AC: 6862 AN: 10548

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47427 AN: 67946

Other (OTH) AF: 0.789 AC: 1666 AN: 2112

Alfa AF: 0.737 Hom.: 135262

Bravo AF: 0.790

Asia WGS AF: 0.892 AC: 3099 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 87% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.6
DANN	Benign	0.41
PhyloP100		-0.071
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: rs887304; hg19: chr12-3757548;