rs72819448
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005208.5(CRYBA1):c.215+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,374,546 control chromosomes in the GnomAD database, including 822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.040 ( 170 hom., cov: 32)
Exomes 𝑓: 0.030 ( 652 hom. )
Consequence
CRYBA1
NM_005208.5 intron
NM_005208.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.184
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 17-29250316-C-T is Benign according to our data. Variant chr17-29250316-C-T is described in ClinVar as [Benign]. Clinvar id is 259671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-29250316-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBA1 | NM_005208.5 | c.215+16C>T | intron_variant | ENST00000225387.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBA1 | ENST00000225387.8 | c.215+16C>T | intron_variant | 1 | NM_005208.5 | P1 | |||
CRYBA1 | ENST00000484605.1 | c.205+16C>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0400 AC: 6075AN: 152032Hom.: 168 Cov.: 32
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GnomAD3 exomes AF: 0.0262 AC: 6590AN: 251394Hom.: 127 AF XY: 0.0254 AC XY: 3450AN XY: 135878
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GnomAD4 exome AF: 0.0298 AC: 36462AN: 1222396Hom.: 652 Cov.: 18 AF XY: 0.0293 AC XY: 18131AN XY: 619716
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GnomAD4 genome AF: 0.0400 AC: 6090AN: 152150Hom.: 170 Cov.: 32 AF XY: 0.0385 AC XY: 2861AN XY: 74386
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Cataract 10 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at