Genetic Variant CRACR2B:p.Ala45Val (chr11-828741-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286606.2(CRACR2B):c.134C>T(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CRACR2B
NM_001286606.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

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]

CRACR2B links:

ENSG00000255108 (HGNC:):

ENSG00000255108 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1366686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRACR2B	NM_001286606.2 link	c.134C>T	p.Ala45Val	missense_variant	Exon 1 of 9	ENST00000525077.2	NP_001273535.1	Q8N4Y2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRACR2B	ENST00000525077.2 link	c.134C>T	p.Ala45Val	missense_variant	Exon 1 of 9	1	NM_001286606.2	ENSP00000435299.1		Q8N4Y2-1
CRACR2B	ENST00000528542.6 link	c.134C>T	p.Ala45Val	missense_variant	Exon 2 of 9	1		ENSP00000432334.1		Q8N4Y2-3

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000844

AC:

AN:

248676

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1461316

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

726956

show subpopulations

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:

0.0000580

Gnomad4 FIN exome

AF:

0.000434

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000826

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.134C>T (p.A45V) alteration is located in exon 2 (coding exon 1) of the CRACR2B gene. This alteration results from a C to T substitution at nucleotide position 134, causing the alanine (A) at amino acid position 45 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

.;.;.;.;.;T

Eigen

Benign

0.069

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D;T;.;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.5

.;.;.;M;M;M

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

N;N;D;N;N;N

REVEL

Benign

0.068

Sift

Uncertain

0.028

D;D;D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;T;T;T

Polyphen

0.99, 0.72

.;.;.;D;D;P

Vest4

0.28, 0.36

MVP

0.79

MPC

0.068

ClinPred

0.10

GERP RS

2.8

Varity_R

0.20

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over