chr1-74707102-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PVS1_StrongPM2BP6_Moderate
The NM_001889.4(CRYZ):c.732+1G>A variant causes a splice donor change. The variant allele was found at a frequency of 0.000281 in 1,553,570 control chromosomes in the GnomAD database, including 1 homozygotes. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
CRYZ
NM_001889.4 splice_donor
NM_001889.4 splice_donor
Scores
4
2
1
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 4.19
Genes affected
CRYZ (HGNC:2419): (crystallin zeta) 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. The former class is also called phylogenetically-restricted crystallins. This gene encodes a taxon-specific crystallin protein which has NADPH-dependent quinone reductase activity distinct from other known quinone reductases. It lacks alcohol dehydrogenase activity although by similarity it is considered a member of the zinc-containing alcohol dehydrogenase family. Unlike other mammalian species, in humans, lens expression is low. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One pseudogene is known to exist. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.102020204 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 1-74707102-C-T is Benign according to our data. Variant chr1-74707102-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 728987.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYZ | NM_001889.4 | c.732+1G>A | splice_donor_variant | ENST00000340866.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYZ | ENST00000340866.10 | c.732+1G>A | splice_donor_variant | 1 | NM_001889.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00146 AC: 221AN: 151224Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000377 AC: 85AN: 225240Hom.: 0 AF XY: 0.000205 AC XY: 25AN XY: 122122
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GnomAD4 exome AF: 0.000153 AC: 214AN: 1402272Hom.: 0 Cov.: 26 AF XY: 0.000116 AC XY: 81AN XY: 699068
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GnomAD4 genome ? AF: 0.00147 AC: 223AN: 151298Hom.: 1 Cov.: 32 AF XY: 0.00131 AC XY: 97AN XY: 73842
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
D;D;D;D
GERP RS
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at