12-3640962-T-C

Variant names:

• chr12-3640962-T-C
• rs4766152
• NM_001144958.2:c.1271+770A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144958.2(CRACR2A):​c.1271+770A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,164 control chromosomes in the GnomAD database, including 23,564 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 0.55 (23564 hom., cov: 33)
• Consequence: CRACR2A NM_001144958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 11 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]

CRACR2A Gene-Disease associations (from GenCC):

• combined immunodeficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2A	NM_001144958.2	MANE Select	c.1271+770A>G		intron	N/A	NP_001138430.1	Q9BSW2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACR2A	ENST00000440314.7	TSL:2 MANE Select	c.1271+770A>G		intron	N/A	ENSP00000409382.2	Q9BSW2-2
	CRACR2A	ENST00000893446.1		c.1271+770A>G		intron	N/A	ENSP00000563505.1
	CRACR2A	ENST00000893447.1		c.1271+770A>G		intron	N/A	ENSP00000563506.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84307 AN: 152046 Hom.: 23551 Cov.: 33

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.554 AC: 84364 AN: 152164 Hom.: 23564 Cov.: 33 AF XY: 0.549 AC XY: 40850 AN XY: 74420

African (AFR) AF: 0.580 AC: 24065 AN: 41490

American (AMR) AF: 0.647 AC: 9899 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2735 AN: 5188

South Asian (SAS) AF: 0.551 AC: 2659 AN: 4824

European-Finnish (FIN) AF: 0.436 AC: 4622 AN: 10592

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36472 AN: 67990

Other (OTH) AF: 0.554 AC: 1169 AN: 2112

Alfa AF: 0.546 Hom.: 74538

Bravo AF: 0.572

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.074
DANN	Benign	0.45
PhyloP100		-2.3
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: rs4766152; hg19: chr12-3750128; COSMIC: COSV107375907;