chr12-3705072-G-A

Position:

• chr12-3705072-G-A

Variant summary

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

The NM_001144958.2(CRACR2A):​c.-36-8037C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,170 control chromosomes in the GnomAD database, including 3,338 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 0.19 (3338 hom., cov: 33)
• Consequence: CRACR2A NM_001144958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.910

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACR2A	NM_001144958.2	c.-36-8037C>T		intron_variant		ENST00000440314.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACR2A	ENST00000440314.7	c.-36-8037C>T		intron_variant		2	NM_001144958.2	P1
CRACR2A	ENST00000252322.1	c.-36-8037C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28988 AN: 152052 Hom.: 3337 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.191 AC: 28993 AN: 152170 Hom.: 3338 Cov.: 33 AF XY: 0.196 AC XY: 14591 AN XY: 74390

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.205

Alfa AF: 0.221 Hom.: 5952

Bravo AF: 0.181

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.1
DANN	Benign	0.44

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: rs10848911; hg19: chr12-3814238;