Genetic Variant CRACR2B:p.Ser248Ile (chr11-830670-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001286606.2(CRACR2B):c.743G>T(p.Ser248Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,546,232 control chromosomes in the GnomAD database, including 371,246 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 33943 hom., cov: 35)

Exomes 𝑓: 0.69 ( 337303 hom. )

Consequence

CRACR2B
NM_001286606.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.301

Publications

42 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.225923E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRACR2B	NM_001286606.2 link	c.743G>T	p.Ser248Ile	missense_variant	Exon 6 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.743G>T	p.Ser248Ile	missense_variant	Exon 6 of 9	1	NM_001286606.2	ENSP00000435299.1		Q8N4Y2-1
CRACR2B	ENST00000528542.6 link	c.743G>T	p.Ser248Ile	missense_variant	Exon 7 of 9	1		ENSP00000432334.1		Q8N4Y2-3

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

100359

AN:

152056

Hom.:

33919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.554

Gnomad AMI

AF:

0.791

Gnomad AMR

AF:

0.725

Gnomad ASJ

AF:

0.452

Gnomad EAS

AF:

0.906

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.621

GnomAD2 exomes

AF:

0.682

AC:

98707

AN:

144806

AF XY:

0.662

show subpopulations

Gnomad AFR exome

AF:

0.549

Gnomad AMR exome

AF:

0.810

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.895

Gnomad FIN exome

AF:

0.774

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.658

GnomAD4 exome

AF:

0.691

AC:

962621

AN:

1394058

Hom.:

337303

Cov.:

AF XY:

0.683

AC XY:

469801

AN XY:

687376

show subpopulations

African (AFR)

AF:

0.534

AC:

16838

AN:

31504

American (AMR)

AF:

0.802

AC:

28553

AN:

35614

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

11546

AN:

25120

East Asian (EAS)

AF:

0.928

AC:

33103

AN:

35674

South Asian (SAS)

AF:

0.483

AC:

38145

AN:

79054

European-Finnish (FIN)

AF:

0.769

AC:

35935

AN:

46728

Middle Eastern (MID)

AF:

0.498

AC:

2339

AN:

4700

European-Non Finnish (NFE)

AF:

0.704

AC:

758347

AN:

1077868

Other (OTH)

AF:

0.654

AC:

37815

AN:

57796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

19830

39661

59491

79322

99152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19316

38632

57948

77264

96580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.660

AC:

100415

AN:

152174

Hom.:

33943

Cov.:

AF XY:

0.661

AC XY:

49141

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.553

AC:

22974

AN:

41538

American (AMR)

AF:

0.726

AC:

11104

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

1568

AN:

3466

East Asian (EAS)

AF:

0.906

AC:

4679

AN:

5164

South Asian (SAS)

AF:

0.487

AC:

2346

AN:

4820

European-Finnish (FIN)

AF:

0.766

AC:

8124

AN:

10610

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.698

AC:

47436

AN:

67958

Other (OTH)

AF:

0.622

AC:

1313

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1765

3531

5296

7062

8827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.678

Hom.:

49779

Bravo

AF:

0.657

TwinsUK

AF:

0.690

AC:

2557

ALSPAC

AF:

0.703

AC:

2710

ESP6500AA

AF:

0.628

AC:

2006

ESP6500EA

AF:

0.721

AC:

4900

ExAC

AF:

0.495

AC:

18946

Asia WGS

AF:

0.690

AC:

2401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.037

.;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.57

.;T;T

MetaRNN

Benign

8.2e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

PhyloP100

0.30

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.046

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.69

P;P;P

Vest4

0.068

MPC

0.041

ClinPred

0.013

GERP RS

1.0

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.15

gMVP

0.070

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over