rs739315

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000496.3(CRYBB2):c.54+152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 645,064 control chromosomes in the GnomAD database, including 59,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11870 hom., cov: 33)

Exomes 𝑓: 0.44 ( 47627 hom. )

Consequence

CRYBB2
NM_000496.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.79

Publications

8 publications found

Variant links:

Genes affected

CRYBB2 (HGNC:2398): (crystallin beta B2) Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group, none in the acidic group). Beta-crystallins form aggregates of different sizes and are able to self-associate to form dimers or to form heterodimers with other beta-crystallins. This gene, a beta basic group member, is part of a gene cluster with beta-A4, beta-B1, and beta-B3. A chain-terminating mutation was found to cause type 2 cerulean cataracts. [provided by RefSeq, Jul 2008]

CRYBB2 Gene-Disease associations (from GenCC):

cataract 3 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
cataract - microcornea syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cerulean cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior subcapsular cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset sutural cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
pulverulent cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
total early-onset cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CRYBB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 22-25221635-A-G is Benign according to our data. Variant chr22-25221635-A-G is described in ClinVar as Benign. ClinVar VariationId is 1258808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB2	NM_000496.3 link	c.54+152A>G		intron_variant	Intron 2 of 5	ENST00000398215.3	NP_000487.1	P43320R4UMM2
CRYBB2	XM_006724141.4 link	c.54+152A>G		intron_variant	Intron 2 of 5		XP_006724204.1	P43320R4UMM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB2	ENST00000398215.3 link	c.54+152A>G		intron_variant	Intron 2 of 5	1	NM_000496.3	ENSP00000381273.2		P43320
CRYBB2	ENST00000651629.1 link	c.54+152A>G		intron_variant	Intron 2 of 5			ENSP00000498905.1		P43320

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59013

AN:

151894

Hom.:

11862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.421

GnomAD4 exome

AF:

0.435

AC:

214661

AN:

493050

Hom.:

47627

AF XY:

0.437

AC XY:

114554

AN XY:

262240

show subpopulations

African (AFR)

AF:

0.273

AC:

3954

AN:

14480

American (AMR)

AF:

0.447

AC:

13717

AN:

30710

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

7169

AN:

15784

East Asian (EAS)

AF:

0.512

AC:

15595

AN:

30442

South Asian (SAS)

AF:

0.447

AC:

23632

AN:

52926

European-Finnish (FIN)

AF:

0.440

AC:

14299

AN:

32512

Middle Eastern (MID)

AF:

0.448

AC:

1423

AN:

3178

European-Non Finnish (NFE)

AF:

0.431

AC:

123112

AN:

285704

Other (OTH)

AF:

0.431

AC:

11760

AN:

27314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

6091

12183

18274

24366

30457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

758

1516

2274

3032

3790

<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:

0.388

AC:

59055

AN:

152014

Hom.:

11870

Cov.:

AF XY:

0.392

AC XY:

29146

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.277

AC:

11484

AN:

41464

American (AMR)

AF:

0.400

AC:

6120

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1601

AN:

3466

East Asian (EAS)

AF:

0.455

AC:

2350

AN:

5168

South Asian (SAS)

AF:

0.450

AC:

2164

AN:

4804

European-Finnish (FIN)

AF:

0.441

AC:

4658

AN:

10558

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.431

AC:

29268

AN:

67948

Other (OTH)

AF:

0.425

AC:

897

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1857

3714

5572

7429

9286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.414

Hom.:

16853

Bravo

AF:

0.380

Asia WGS

AF:

0.473

AC:

1643

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 28, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.11

(source)

DANN

Benign

0.58

PhyloP100

-1.8

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over