chr17-29253738-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005208.5(CRYBA1):c.456C>T(p.Gly152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,442 control chromosomes in the GnomAD database, including 33,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.22 ( 4298 hom., cov: 32)
Exomes 𝑓: 0.19 ( 28967 hom. )
Consequence
CRYBA1
NM_005208.5 synonymous
NM_005208.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.811
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=-0.58).
BP6
Variant 17-29253738-C-T is Benign according to our data. Variant chr17-29253738-C-T is described in ClinVar as [Benign]. Clinvar id is 259672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-29253738-C-T is described in Lovd as [Benign]. Variant chr17-29253738-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.811 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBA1 | NM_005208.5 | c.456C>T | p.Gly152= | synonymous_variant | 5/6 | ENST00000225387.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBA1 | ENST00000225387.8 | c.456C>T | p.Gly152= | synonymous_variant | 5/6 | 1 | NM_005208.5 | P1 | |
CRYBA1 | ENST00000484605.1 | c.*77C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.224 AC: 34102AN: 151948Hom.: 4290 Cov.: 32
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GnomAD3 exomes AF: 0.213 AC: 53634AN: 251434Hom.: 6651 AF XY: 0.217 AC XY: 29468AN XY: 135898
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GnomAD4 exome AF: 0.190 AC: 278006AN: 1461374Hom.: 28967 Cov.: 33 AF XY: 0.193 AC XY: 140604AN XY: 727028
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GnomAD4 genome AF: 0.225 AC: 34152AN: 152068Hom.: 4298 Cov.: 32 AF XY: 0.227 AC XY: 16890AN XY: 74346
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
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 | Apr 02, 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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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