chr22-25201402-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_004076.5(CRYBB3):c.6G>A(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000774 in 1,613,314 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 5 hom. )
Consequence
CRYBB3
NM_004076.5 synonymous
NM_004076.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.42
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 22-25201402-G-A is Benign according to our data. Variant chr22-25201402-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 703368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-25201402-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-4.42 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00171 (260/152240) while in subpopulation AFR AF= 0.004 (166/41542). AF 95% confidence interval is 0.0035. There are 0 homozygotes in gnomad4. There are 123 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 5 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBB3 | NM_004076.5 | c.6G>A | p.Ala2= | synonymous_variant | 2/6 | ENST00000215855.7 | |
CRYBB3 | XM_047441147.1 | c.6G>A | p.Ala2= | synonymous_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBB3 | ENST00000215855.7 | c.6G>A | p.Ala2= | synonymous_variant | 2/6 | 1 | NM_004076.5 | P1 | |
CRYBB3 | ENST00000404334.1 | c.6G>A | p.Ala2= | synonymous_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00170 AC: 259AN: 152122Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00119 AC: 299AN: 251400Hom.: 1 AF XY: 0.000993 AC XY: 135AN XY: 135898
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GnomAD4 exome AF: 0.000677 AC: 989AN: 1461074Hom.: 5 Cov.: 34 AF XY: 0.000654 AC XY: 475AN XY: 726840
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GnomAD4 genome AF: 0.00171 AC: 260AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00165 AC XY: 123AN XY: 74428
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | CRYBB3: BP4, BP7 - |
Cataract 22 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2022 | - - |
Computational scores
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at