chr22-26629915-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001886.3(CRYBA4):​c.444-425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 135,806 control chromosomes in the GnomAD database, including 4,067 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4067 hom., cov: 32)

Consequence

CRYBA4
NM_001886.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.543

Publications

5 publications found
Variant links:
Genes affected
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]
CRYBA4 Gene-Disease associations (from GenCC):
  • cataract 23
    Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • cataract - microcornea syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • early-onset lamellar cataract
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRYBA4NM_001886.3 linkc.444-425T>C intron_variant Intron 5 of 5 ENST00000354760.4 NP_001877.1 P53673A0A097PIJ6
CRYBA4XM_006724140.4 linkc.459-425T>C intron_variant Intron 7 of 7 XP_006724203.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRYBA4ENST00000354760.4 linkc.444-425T>C intron_variant Intron 5 of 5 1 NM_001886.3 ENSP00000346805.3 P53673
CRYBA4ENST00000466315.1 linkn.341-425T>C intron_variant Intron 4 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.241
AC:
32644
AN:
135682
Hom.:
4056
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.351
Gnomad AMI
AF:
0.209
Gnomad AMR
AF:
0.237
Gnomad ASJ
AF:
0.216
Gnomad EAS
AF:
0.418
Gnomad SAS
AF:
0.309
Gnomad FIN
AF:
0.175
Gnomad MID
AF:
0.158
Gnomad NFE
AF:
0.166
Gnomad OTH
AF:
0.243
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.241
AC:
32681
AN:
135806
Hom.:
4067
Cov.:
32
AF XY:
0.243
AC XY:
15992
AN XY:
65754
show subpopulations
African (AFR)
AF:
0.351
AC:
13399
AN:
38144
American (AMR)
AF:
0.237
AC:
3078
AN:
12970
Ashkenazi Jewish (ASJ)
AF:
0.216
AC:
685
AN:
3170
East Asian (EAS)
AF:
0.419
AC:
1995
AN:
4760
South Asian (SAS)
AF:
0.308
AC:
1242
AN:
4026
European-Finnish (FIN)
AF:
0.175
AC:
1456
AN:
8324
Middle Eastern (MID)
AF:
0.158
AC:
43
AN:
272
European-Non Finnish (NFE)
AF:
0.165
AC:
10179
AN:
61516
Other (OTH)
AF:
0.240
AC:
426
AN:
1774
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.524
Heterozygous variant carriers
0
1294
2588
3882
5176
6470
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
344
688
1032
1376
1720
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.190
Hom.:
379
Bravo
AF:
0.224
Asia WGS
AF:
0.254
AC:
882
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.93
DANN
Benign
0.21
PhyloP100
-0.54
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs5752359; hg19: chr22-27025879; API