rs13055430

Variant names:

Variant summary

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

The NM_004076.5(CRYBB3):c.471-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,610,468 control chromosomes in the GnomAD database, including 6,212 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 396 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5816 hom. )

Consequence

CRYBB3
NM_004076.5 splice_region, intron

Scores

Splicing: ADA: 0.0004944

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0380

Publications

6 publications found

Variant links:

Genes affected

CRYBB3 (HGNC:2400): (crystallin beta B3) 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-B2. Mutations in this gene result in cataract congenital nuclear autosomal recessive type 2. [provided by RefSeq, Feb 2013]

CRYBB3 Gene-Disease associations (from GenCC):

cataract 22 multiple types
Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
early-onset anterior polar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset non-syndromic cataract
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CRYBB3 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=-0.57).

BP6

Variant 22-25207041-C-T is Benign according to our data. Variant chr22-25207041-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB3	NM_004076.5 link	c.471-6C>T		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000215855.7	NP_004067.1	P26998
CRYBB3	XM_047441147.1 link	c.471-6C>T		splice_region_variant, intron_variant	Intron 4 of 4		XP_047297103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB3	ENST00000215855.7 link	c.471-6C>T		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_004076.5	ENSP00000215855.2		P26998
CRYBB3	ENST00000404334.1 link	c.328-6C>T		splice_region_variant, intron_variant	Intron 4 of 4	3		ENSP00000386123.1		B1AHR5

Frequencies

GnomAD3 genomes

AF:

0.0652

AC:

9919

AN:

152094

Hom.:

394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0462

Gnomad ASJ

AF:

0.0732

Gnomad EAS

AF:

0.0292

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0855

Gnomad OTH

AF:

0.0522

GnomAD2 exomes

AF:

0.0798

AC:

19874

AN:

249134

AF XY:

0.0846

show subpopulations

Gnomad AFR exome

AF:

0.0217

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.0720

Gnomad EAS exome

AF:

0.0317

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.0852

Gnomad OTH exome

AF:

0.0788

GnomAD4 exome

AF:

0.0842

AC:

122807

AN:

1458256

Hom.:

5816

Cov.:

AF XY:

0.0865

AC XY:

62804

AN XY:

725714

show subpopulations

African (AFR)

AF:

0.0193

AC:

644

AN:

33410

American (AMR)

AF:

0.0415

AC:

1856

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0710

AC:

1853

AN:

26114

East Asian (EAS)

AF:

0.0209

AC:

829

AN:

39692

South Asian (SAS)

AF:

0.141

AC:

12163

AN:

86202

European-Finnish (FIN)

AF:

0.115

AC:

6113

AN:

53196

Middle Eastern (MID)

AF:

0.0529

AC:

305

AN:

5766

European-Non Finnish (NFE)

AF:

0.0847

AC:

93908

AN:

1108864

Other (OTH)

AF:

0.0852

AC:

5136

AN:

60292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

5437

10874

16310

21747

27184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0652

AC:

9930

AN:

152212

Hom.:

396

Cov.:

AF XY:

0.0669

AC XY:

4977

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0221

AC:

919

AN:

41554

American (AMR)

AF:

0.0463

AC:

708

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0732

AC:

254

AN:

3472

East Asian (EAS)

AF:

0.0290

AC:

150

AN:

5164

South Asian (SAS)

AF:

0.150

AC:

726

AN:

4828

European-Finnish (FIN)

AF:

0.112

AC:

1187

AN:

10592

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0855

AC:

5816

AN:

67992

Other (OTH)

AF:

0.0550

AC:

116

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

486

971

1457

1942

2428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0746

Hom.:

455

Bravo

AF:

0.0558

Asia WGS

AF:

0.100

AC:

348

AN:

3478

EpiCase

AF:

0.0807

EpiControl

AF:

0.0755

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital nuclear cataract

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cataract 22 multiple types

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.57

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00049

dbscSNV1_RF

Benign

0.028

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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rs13055430

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