12-3759002-C-T

Position:

• chr12-3759002-C-T

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, non coding transcript 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, non_coding_transcript
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000514026.2	n.255+5563G>A		intron_variant, non_coding_transcript_variant		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;