rs76323117
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005210.4(CRYGB):c.175C>T(p.Arg59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,102 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 14 hom., cov: 31)
Exomes 𝑓: 0.00072 ( 9 hom. )
Consequence
CRYGB
NM_005210.4 missense
NM_005210.4 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 1.03
Genes affected
CRYGB (HGNC:2409): (crystallin gamma B) 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. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [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 (MetaRNN=0.012019426).
BP6
Variant 2-208145851-G-A is Benign according to our data. Variant chr2-208145851-G-A is described in ClinVar as [Benign]. Clinvar id is 474170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0069 (1050/152234) while in subpopulation AFR AF= 0.0242 (1006/41538). AF 95% confidence interval is 0.023. There are 14 homozygotes in gnomad4. There are 527 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1050 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRYGB | NM_005210.4 | c.175C>T | p.Arg59Trp | missense_variant | 2/3 | ENST00000260988.5 | NP_005201.2 | |
CRYGB | XM_017003402.2 | c.175C>T | p.Arg59Trp | missense_variant | 2/3 | XP_016858891.1 | ||
LOC100507443 | NR_038437.1 | n.221+8672G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRYGB | ENST00000260988.5 | c.175C>T | p.Arg59Trp | missense_variant | 2/3 | 1 | NM_005210.4 | ENSP00000260988.4 |
Frequencies
GnomAD3 genomes AF: 0.00690 AC: 1050AN: 152114Hom.: 14 Cov.: 31
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GnomAD3 exomes AF: 0.00172 AC: 432AN: 251334Hom.: 3 AF XY: 0.00124 AC XY: 169AN XY: 135880
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GnomAD4 exome AF: 0.000722 AC: 1055AN: 1461868Hom.: 9 Cov.: 59 AF XY: 0.000602 AC XY: 438AN XY: 727234
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GnomAD4 genome AF: 0.00690 AC: 1050AN: 152234Hom.: 14 Cov.: 31 AF XY: 0.00708 AC XY: 527AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Cataract 39 multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 04, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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