rs13055430

Positions:

chr22-25207041-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CRYBB3	NM_004076.5 linkuse as main transcript	c.471-6C>T		splice_region_variant, intron_variant		ENST00000215855.7	NP_004067.1	P26998
CRYBB3	XM_047441147.1 linkuse as main transcript	c.471-6C>T		splice_region_variant, intron_variant			XP_047297103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBB3	ENST00000215855.7 linkuse as main transcript	c.471-6C>T		splice_region_variant, intron_variant		1	NM_004076.5	ENSP00000215855.2		P26998
CRYBB3	ENST00000404334.1 linkuse as main transcript	c.328-6C>T		splice_region_variant, intron_variant		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

GnomAD3 exomes

AF:

0.0798

AC:

19874

AN:

249134

Hom.:

960

AF XY:

0.0846

AC XY:

11414

AN XY:

134966

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 SAS exome

AF:

0.140

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

Gnomad4 AFR exome

AF:

0.0193

Gnomad4 AMR exome

AF:

0.0415

Gnomad4 ASJ exome

AF:

0.0710

Gnomad4 EAS exome

AF:

0.0209

Gnomad4 SAS exome

AF:

0.141

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.0847

Gnomad4 OTH exome

AF:

0.0852

GnomAD4 genome

AF:

0.0652

AC:

9930

AN:

152212

Hom.:

396

Cov.:

AF XY:

0.0669

AC XY:

4977

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.0463

Gnomad4 ASJ

AF:

0.0732

Gnomad4 EAS

AF:

0.0290

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.0855

Gnomad4 OTH

AF:

0.0550

Alfa

AF:

0.0755

Hom.:

340

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	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. -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital nuclear cataract

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cataract 22 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over