chr17-29249185-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_005208.5(CRYBA1):c.75G>A(p.Pro25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,611,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
CRYBA1
NM_005208.5 synonymous
NM_005208.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.722
Genes affected
CRYBA1 (HGNC:2394): (crystallin beta A1) 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 acidic group member, encodes two proteins (crystallin, beta A3 and crystallin, beta A1) from a single mRNA, the latter protein is 17 aa shorter than crystallin, beta A3 and is generated by use of an alternate translation initiation site. Deletion of exons 3 and 4 causes the autosomal dominant disease 'zonular cataract with sutural opacities'. [provided by RefSeq, Jul 2008]
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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=-0.63).
BP6
?
Variant 17-29249185-G-A is Benign according to our data. Variant chr17-29249185-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1166238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.722 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000375 (57/151868) while in subpopulation AFR AF= 0.00123 (51/41378). AF 95% confidence interval is 0.000962. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd at 57 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBA1 | NM_005208.5 | c.75G>A | p.Pro25= | synonymous_variant | 2/6 | ENST00000225387.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBA1 | ENST00000225387.8 | c.75G>A | p.Pro25= | synonymous_variant | 2/6 | 1 | NM_005208.5 | P1 | |
CRYBA1 | ENST00000484605.1 | c.66G>A | p.Pro22= | synonymous_variant, NMD_transcript_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000375 AC: 57AN: 151868Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251262Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135832
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GnomAD4 exome AF: 0.0000425 AC: 62AN: 1460050Hom.: 0 Cov.: 29 AF XY: 0.0000427 AC XY: 31AN XY: 726476
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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
CRYBA1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 12, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Cataract 10 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at