Genetic Variant CRACR2B:p.Trp161* (chr11-830009-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001286606.2(CRACR2B):c.482G>A(p.Trp161*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,572,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CRACR2B
NM_001286606.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.15

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286606.2. 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
	CRACR2B	NM_001286606.2	MANE Select	c.482G>A	p.Trp161*	stop_gained	Exon 4 of 9	NP_001273535.1	Q8N4Y2-1
	CRACR2B	NM_173584.4		c.482G>A	p.Trp161*	stop_gained	Exon 4 of 8	NP_775855.3	Q8N4Y2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRACR2B	ENST00000525077.2	TSL:1 MANE Select	c.482G>A	p.Trp161*	stop_gained	Exon 4 of 9	ENSP00000435299.1	Q8N4Y2-1
CRACR2B	ENST00000450448.5	TSL:1	c.482G>A	p.Trp161*	stop_gained	Exon 4 of 8	ENSP00000409256.1	Q8N4Y2-3
CRACR2B	ENST00000528542.6	TSL:1	c.482G>A	p.Trp161*	stop_gained	Exon 5 of 9	ENSP00000432334.1	Q8N4Y2-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152260

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000547

AC:

AN:

182684

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1419788

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

704474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32662

American (AMR)

AF:

0.00

AC:

AN:

42050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25600

East Asian (EAS)

AF:

0.00

AC:

AN:

37910

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097312

Other (OTH)

AF:

0.00

AC:

AN:

59006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ExAC

AF:

0.00000847

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.54

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.80

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

PhyloP100

3.2

Vest4

0.14

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=23/177

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over