22-26607993-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001887.4(CRYBB1):​c.328C>G​(p.Arg110Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R110C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CRYBB1
NM_001887.4 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.08
Variant links:
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]
CRYBA4 (HGNC:2396): (crystallin beta A4) 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, is part of a gene cluster with beta-B1, beta-B2, and beta-B3. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRYBB1NM_001887.4 linkc.328C>G p.Arg110Gly missense_variant Exon 4 of 6 ENST00000647684.1 NP_001878.1 P53674
CRYBB1XM_011529899.4 linkc.328C>G p.Arg110Gly missense_variant Exon 4 of 6 XP_011528201.1 P53674
CRYBA4XM_006724140.4 linkc.-67G>C 5_prime_UTR_variant Exon 3 of 8 XP_006724203.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRYBB1ENST00000647684.1 linkc.328C>G p.Arg110Gly missense_variant Exon 4 of 6 NM_001887.4 ENSP00000497249.1 P53674
CRYBB1ENST00000647569.1 linkn.140C>G non_coding_transcript_exon_variant Exon 2 of 3
ENSG00000286326ENST00000668614.1 linkn.228G>C non_coding_transcript_exon_variant Exon 2 of 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T;T
Eigen
Benign
-0.047
Eigen_PC
Benign
-0.0096
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.81
.;T
M_CAP
Benign
0.081
D
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.0
.;D
REVEL
Uncertain
0.39
Sift
Benign
0.068
.;T
Sift4G
Benign
0.30
.;T
Polyphen
0.12
B;B
Vest4
0.69
MutPred
0.52
Loss of catalytic residue at R110 (P = 0.0216);Loss of catalytic residue at R110 (P = 0.0216);
MVP
0.86
MPC
0.43
ClinPred
0.82
D
GERP RS
2.5
Varity_R
0.38
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147206089; hg19: chr22-27003957; API