12-3640962-T-C

Position:

• chr12-3640962-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRACR2A	NM_001144958.2	c.1271+770A>G		intron_variant		ENST00000440314.7	NP_001138430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRACR2A	ENST00000440314.7	c.1271+770A>G		intron_variant		2	NM_001144958.2	ENSP00000409382	P1
CRACR2A	ENST00000535292.1	c.238-183A>G		intron_variant		5		ENSP00000438777
CRACR2A	ENST00000333750.9	c.*265+770A>G		intron_variant, NMD_transcript_variant		2		ENSP00000331047

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

Gnomad4 AFR AF: 0.580

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.554

Alfa AF: 0.541 Hom.: 48593

Bravo AF: 0.572

Asia WGS AF: 0.536 AC: 1863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.074
DANN	Benign	0.45

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: rs4766152; hg19: chr12-3750128;