12-3627774-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001144958.2(CRACR2A):c.1736-68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,433,278 control chromosomes in the GnomAD database, including 23,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2293 hom., cov: 31)
  • Exomes 𝑓: 0.18 (21113 hom.)
• Consequence: CRACR2A NM_001144958.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.80

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-3627774-C-T is Benign according to our data. Variant chr12-3627774-C-T is described in ClinVar as [Benign]. Clinvar id is 2688160.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACR2A	NM_001144958.2	c.1736-68G>A		intron_variant		ENST00000440314.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000440314.7	c.1736-68G>A		intron_variant		2	NM_001144958.2	P1
CRACR2A	ENST00000333750.9	c.*733-68G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24038 AN: 152044 Hom.: 2293 Cov.: 31

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0985

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.175 AC: 224744 AN: 1281116 Hom.: 21113 AF XY: 0.174 AC XY: 110764 AN XY: 637842

Gnomad4 AFR exome AF: 0.0807

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.295

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.158 AC: 24046 AN: 152162 Hom.: 2293 Cov.: 31 AF XY: 0.166 AC XY: 12334 AN XY: 74366

Gnomad4 AFR AF: 0.0873

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0985

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.158

Alfa AF: 0.158 Hom.: 1884

Bravo AF: 0.155

Asia WGS AF: 0.221 AC: 764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0030
Dann	Benign	0.35

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: rs17836183; hg19: chr12-3736940;