11-829393-C-T

Variant names:

• chr11-829393-C-T
• rs200792273
• NM_001286606.2:c.311C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286606.2(CRACR2B):​c.311C>T​(p.Ala104Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRACR2B NM_001286606.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864

Genes affected

CRACR2B (HGNC:28703): (calcium release activated channel regulator 2B) Predicted to enable calcium ion binding activity. Involved in store-operated calcium entry. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255108 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056773007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRACR2B	NM_001286606.2	c.311C>T	p.Ala104Val	missense_variant	Exon 3 of 9	ENST00000525077.2	NP_001273535.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRACR2B	ENST00000525077.2	c.311C>T	p.Ala104Val	missense_variant	Exon 3 of 9	1	NM_001286606.2	ENSP00000435299.1
CRACR2B	ENST00000528542.6	c.311C>T	p.Ala104Val	missense_variant	Exon 4 of 9	1		ENSP00000432334.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457782 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.52	.;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.12	B;B;B
Vest4		0.090
MutPred		0.23		Loss of disorder (P = 0.0934);Loss of disorder (P = 0.0934);Loss of disorder (P = 0.0934);
MVP		0.15
MPC		0.028
ClinPred		0.049	T
GERP RS		-2.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.058
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs200792273; hg19: chr11-829393;