rs4049505

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.449+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,613,564 control chromosomes in the GnomAD database, including 388,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 39477 hom., cov: 35)

Exomes 𝑓: 0.69 ( 349049 hom. )

Consequence

CRYBB2
NM_000496.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.60

Publications

6 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=-0.87).

BP6

Variant 22-25229587-G-A is Benign according to our data. Variant chr22-25229587-G-A is described in ClinVar as [Benign]. Clinvar id is 256282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB2	NM_000496.3 link	c.449+9G>A		intron_variant	Intron 5 of 5	ENST00000398215.3	NP_000487.1	P43320R4UMM2
CRYBB2	XM_006724141.4 link	c.449+9G>A		intron_variant	Intron 5 of 5		XP_006724204.1	P43320R4UMM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB2	ENST00000398215.3 link	c.449+9G>A		intron_variant	Intron 5 of 5	1	NM_000496.3	ENSP00000381273.2		P43320
CRYBB2	ENST00000651629.1 link	c.449+9G>A		intron_variant	Intron 5 of 5			ENSP00000498905.1		P43320

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108986

AN:

152134

Hom.:

39456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.700

Gnomad AMR

AF:

0.699

Gnomad ASJ

AF:

0.672

Gnomad EAS

AF:

0.958

Gnomad SAS

AF:

0.803

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.764

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.726

GnomAD2 exomes

AF:

0.726

AC:

181914

AN:

250512

AF XY:

0.724

show subpopulations

Gnomad AFR exome

AF:

0.787

Gnomad AMR exome

AF:

0.777

Gnomad ASJ exome

AF:

0.682

Gnomad EAS exome

AF:

0.956

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.694

GnomAD4 exome

AF:

0.688

AC:

1005378

AN:

1461312

Hom.:

349049

Cov.:

AF XY:

0.691

AC XY:

502014

AN XY:

726946

show subpopulations

African (AFR)

AF:

0.787

AC:

26335

AN:

33472

American (AMR)

AF:

0.769

AC:

34347

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

17737

AN:

26128

East Asian (EAS)

AF:

0.961

AC:

38154

AN:

39696

South Asian (SAS)

AF:

0.783

AC:

67537

AN:

86214

European-Finnish (FIN)

AF:

0.649

AC:

34673

AN:

53386

Middle Eastern (MID)

AF:

0.761

AC:

4390

AN:

5768

European-Non Finnish (NFE)

AF:

0.665

AC:

739724

AN:

1111606

Other (OTH)

AF:

0.704

AC:

42481

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

19112

38224

57337

76449

95561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.716

AC:

109059

AN:

152252

Hom.:

39477

Cov.:

AF XY:

0.716

AC XY:

53306

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.783

AC:

32513

AN:

41548

American (AMR)

AF:

0.699

AC:

10702

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.672

AC:

2329

AN:

3468

East Asian (EAS)

AF:

0.958

AC:

4964

AN:

5182

South Asian (SAS)

AF:

0.802

AC:

3875

AN:

4830

European-Finnish (FIN)

AF:

0.645

AC:

6838

AN:

10608

Middle Eastern (MID)

AF:

0.757

AC:

221

AN:

292

European-Non Finnish (NFE)

AF:

0.668

AC:

45439

AN:

67996

Other (OTH)

AF:

0.728

AC:

1540

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1645

3290

4935

6580

8225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.708

Hom.:

19831

Bravo

AF:

0.728

Asia WGS

AF:

0.859

AC:

2988

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

(source)

DANN

Benign

0.63

PhyloP100

-1.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs4049505

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