rs8140949

Variant names:

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.483G>A(p.Gly161Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.236 in 1,613,704 control chromosomes in the GnomAD database, including 48,773 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5024 hom., cov: 31)

Exomes 𝑓: 0.23 ( 43749 hom. )

Consequence

CRYBB2
NM_000496.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.61

Publications

20 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=-0.52).

BP6

Variant 22-25231637-G-A is Benign according to our data. Variant chr22-25231637-G-A is described in ClinVar as Benign. ClinVar VariationId is 256283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB2	NM_000496.3 link	c.483G>A	p.Gly161Gly	synonymous_variant	Exon 6 of 6	ENST00000398215.3	NP_000487.1	P43320R4UMM2
CRYBB2	XM_006724141.4 link	c.483G>A	p.Gly161Gly	synonymous_variant	Exon 6 of 6		XP_006724204.1	P43320R4UMM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB2	ENST00000398215.3 link	c.483G>A	p.Gly161Gly	synonymous_variant	Exon 6 of 6	1	NM_000496.3	ENSP00000381273.2		P43320
CRYBB2	ENST00000651629.1 link	c.483G>A	p.Gly161Gly	synonymous_variant	Exon 6 of 6			ENSP00000498905.1		P43320

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37829

AN:

151894

Hom.:

5019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.421

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.180

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.216

Gnomad OTH

AF:

0.261

GnomAD2 exomes

AF:

0.277

AC:

69048

AN:

249516

AF XY:

0.280

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.271

Gnomad EAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.188

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.235

AC:

343437

AN:

1461692

Hom.:

43749

Cov.:

AF XY:

0.241

AC XY:

175412

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.276

AC:

9255

AN:

33476

American (AMR)

AF:

0.306

AC:

13690

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

6992

AN:

26134

East Asian (EAS)

AF:

0.410

AC:

16259

AN:

39698

South Asian (SAS)

AF:

0.428

AC:

36914

AN:

86248

European-Finnish (FIN)

AF:

0.189

AC:

10075

AN:

53420

Middle Eastern (MID)

AF:

0.292

AC:

1684

AN:

5766

European-Non Finnish (NFE)

AF:

0.210

AC:

233349

AN:

1111838

Other (OTH)

AF:

0.252

AC:

15219

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

15242

30485

45727

60970

76212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8394

16788

25182

33576

41970

<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:

0.249

AC:

37852

AN:

152012

Hom.:

5024

Cov.:

AF XY:

0.251

AC XY:

18636

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.272

AC:

11297

AN:

41460

American (AMR)

AF:

0.250

AC:

3821

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3466

East Asian (EAS)

AF:

0.420

AC:

2161

AN:

5140

South Asian (SAS)

AF:

0.449

AC:

2160

AN:

4810

European-Finnish (FIN)

AF:

0.180

AC:

1906

AN:

10594

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14675

AN:

67954

Other (OTH)

AF:

0.267

AC:

564

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1419

2839

4258

5678

7097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.231

Hom.:

1722

Bravo

AF:

0.256

Asia WGS

AF:

0.409

AC:

1421

AN:

3478

EpiCase

AF:

0.223

EpiControl

AF:

0.227

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 3 multiple types

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.52

CADD

Benign

4.7

(source)

DANN

Benign

0.37

PhyloP100

3.6

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