chr22-26601947-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001887.4(CRYBB1):c.507C>T(p.Asp169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,372 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 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
CRYBB1
NM_001887.4 synonymous
NM_001887.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.55
Genes affected
CRYBB1 (HGNC:2397): (crystallin beta B1) 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, undergoes extensive cleavage at its N-terminal extension during lens maturation. It is also a member of a gene cluster with beta-A4, beta-B2, and beta-B3. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 22-26601947-G-A is Benign according to our data. Variant chr22-26601947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1152829.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-2.55 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYBB1 | NM_001887.4 | c.507C>T | p.Asp169= | synonymous_variant | 5/6 | ENST00000647684.1 | |
CRYBB1 | XM_011529899.4 | c.507C>T | p.Asp169= | synonymous_variant | 5/6 | ||
CRYBA4 | XM_006724140.4 | c.-239+4864G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYBB1 | ENST00000647684.1 | c.507C>T | p.Asp169= | synonymous_variant | 5/6 | NM_001887.4 | P1 | ||
ENST00000668614.1 | n.56+4864G>A | intron_variant, non_coding_transcript_variant | |||||||
CRYBB1 | ENST00000647569.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152070Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251322Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135822
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461184Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 726918
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152188Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74408
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cataract 17 multiple types Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
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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