22-25201364-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004076.5(CRYBB3):c.-20-13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,611,378 control chromosomes in the GnomAD database, including 238,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28865 hom., cov: 32)

Exomes 𝑓: 0.53 ( 209447 hom. )

Consequence

CRYBB3
NM_004076.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.341

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=-0.92).

BP6

Variant 22-25201364-T-C is Benign according to our data. Variant chr22-25201364-T-C is described in ClinVar as [Benign]. Clinvar id is 340947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB3	NM_004076.5 link	c.-20-13T>C		intron_variant	Intron 1 of 5	ENST00000215855.7	NP_004067.1	P26998
CRYBB3	XM_047441147.1 link	c.-33T>C		5_prime_UTR_variant	Exon 1 of 5		XP_047297103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB3	ENST00000215855.7 link	c.-20-13T>C		intron_variant	Intron 1 of 5	1	NM_004076.5	ENSP00000215855.2		P26998
CRYBB3	ENST00000404334.1 link	c.-16-17T>C		intron_variant	Intron 1 of 4	3		ENSP00000386123.1		B1AHR5

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91641

AN:

151984

Hom.:

28801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.595

GnomAD3 exomes

AF:

0.564

AC:

141604

AN:

251264

Hom.:

40931

AF XY:

0.553

AC XY:

75141

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.788

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.683

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.472

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.532

AC:

777059

AN:

1459276

Hom.:

209447

Cov.:

107

AF XY:

0.531

AC XY:

385342

AN XY:

725938

show subpopulations

Gnomad4 AFR exome

AF:

0.800

Gnomad4 AMR exome

AF:

0.641

Gnomad4 ASJ exome

AF:

0.569

Gnomad4 EAS exome

AF:

0.660

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.471

Gnomad4 NFE exome

AF:

0.517

Gnomad4 OTH exome

AF:

0.557

GnomAD4 genome

AF:

0.603

AC:

91761

AN:

152102

Hom.:

28865

Cov.:

AF XY:

0.602

AC XY:

44781

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.788

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.684

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.515

Gnomad4 OTH

AF:

0.600

Alfa

AF:

0.534

Hom.:

27691

Bravo

AF:

0.628

Asia WGS

AF:

0.645

AC:

2244

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

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. -

Congenital nuclear cataract

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cataract 22 multiple types

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

-0.92

CADD

Benign

8.8

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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