12-3759002-C-T

Variant names:

• chr12-3759002-C-T
• rs10744625
• ENST00000514026.2:n.255+5563G>A

Variant summary

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

The ENST00000514026.2(CRACR2A):​n.255+5563G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,220 control chromosomes in the GnomAD database, including 52,408 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 0.83 (52408 hom., cov: 32)
• Consequence: CRACR2A ENST00000514026.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRACR2A	ENST00000514026.2	n.255+5563G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125605 AN: 152102 Hom.: 52379 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.887

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.826 AC: 125685 AN: 152220 Hom.: 52408 Cov.: 32 AF XY: 0.826 AC XY: 61506 AN XY: 74436

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.887

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.822

Alfa AF: 0.815 Hom.: 20146

Bravo AF: 0.807

Asia WGS AF: 0.805 AC: 2799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.5
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10744625; hg19: chr12-3868168;