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1-74710113-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001889.4(CRYZ):c.615C>T(p.Tyr205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00899 in 1,612,774 control chromosomes in the GnomAD database, including 924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.045 ( 500 hom., cov: 33)
Exomes 𝑓: 0.0052 ( 424 hom. )

Consequence

CRYZ
NM_001889.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250
Variant links:
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 Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-74710113-G-A is Benign according to our data. Variant chr1-74710113-G-A is described in ClinVar as [Benign]. Clinvar id is 3037236.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.025 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CRYZNM_001889.4 linkuse as main transcriptc.615C>T p.Tyr205= synonymous_variant 6/9 ENST00000340866.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CRYZENST00000340866.10 linkuse as main transcriptc.615C>T p.Tyr205= synonymous_variant 6/91 NM_001889.4 P1Q08257-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0452
AC:
6876
AN:
152046
Hom.:
499
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.153
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0181
Gnomad ASJ
AF:
0.0363
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.000956
Gnomad OTH
AF:
0.0282
GnomAD3 exomes
AF:
0.0130
AC:
3260
AN:
250406
Hom.:
200
AF XY:
0.0103
AC XY:
1392
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.153
Gnomad AMR exome
AF:
0.00620
Gnomad ASJ exome
AF:
0.0377
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000524
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000990
Gnomad OTH exome
AF:
0.00904
GnomAD4 exome
AF:
0.00521
AC:
7609
AN:
1460610
Hom.:
424
Cov.:
30
AF XY:
0.00465
AC XY:
3381
AN XY:
726624
show subpopulations
Gnomad4 AFR exome
AF:
0.153
Gnomad4 AMR exome
AF:
0.00740
Gnomad4 ASJ exome
AF:
0.0345
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000441
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.000404
Gnomad4 OTH exome
AF:
0.0122
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0453
AC:
6891
AN:
152164
Hom.:
500
Cov.:
33
AF XY:
0.0450
AC XY:
3346
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.153
Gnomad4 AMR
AF:
0.0180
Gnomad4 ASJ
AF:
0.0363
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000956
Gnomad4 OTH
AF:
0.0279
Alfa
AF:
0.0371
Hom.:
2463
Bravo
AF:
0.0510
Asia WGS
AF:
0.00895
AC:
32
AN:
3476
EpiCase
AF:
0.00169
EpiControl
AF:
0.00172

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CRYZ-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesNov 06, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
3.1
Dann
Benign
0.28

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: rs57413593; hg19: chr1-75175797; API