chr22-25201364-T-C
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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 splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
NM_004076.5 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.341
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]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBB3 | NM_004076.5 | c.-20-13T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000215855.7 | |||
CRYBB3 | XM_047441147.1 | c.-33T>C | 5_prime_UTR_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBB3 | ENST00000215855.7 | c.-20-13T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004076.5 | P1 | |||
CRYBB3 | ENST00000404334.1 | c.-16-17T>C | splice_polypyrimidine_tract_variant, intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.603 AC: 91641AN: 151984Hom.: 28801 Cov.: 32
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GnomAD3 exomes AF: 0.564 AC: 141604AN: 251264Hom.: 40931 AF XY: 0.553 AC XY: 75141AN XY: 135836
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GnomAD4 exome AF: 0.532 AC: 777059AN: 1459276Hom.: 209447 Cov.: 107 AF XY: 0.531 AC XY: 385342AN XY: 725938
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GnomAD4 genome AF: 0.603 AC: 91761AN: 152102Hom.: 28865 Cov.: 32 AF XY: 0.602 AC XY: 44781AN XY: 74350
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Congenital nuclear cataract Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
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. - |
Cataract 22 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at