Variant 1-74706968-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001889.4(CRYZ):c.759A>G(p.Glu253Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,612,554 control chromosomes in the GnomAD database, including 1,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.030 ( 95 hom., cov: 31)

Exomes 𝑓: 0.041 ( 1391 hom. )

Consequence

CRYZ
NM_001889.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.743

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]

CRYZ links:

CRYZ (HGNC:):

CRYZ links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-74706968-T-C is Benign according to our data. Variant chr1-74706968-T-C is described in ClinVar as [Benign]. Clinvar id is 3057215.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.743 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0299 (4547/152070) while in subpopulation NFE AF= 0.0462 (3141/67920). AF 95% confidence interval is 0.0449. There are 95 homozygotes in gnomad4. There are 2058 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 95 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYZ	NM_001889.4 linkuse as main transcript	c.759A>G	p.Glu253Glu	synonymous_variant	8/9	ENST00000340866.10	NP_001880.2	Q08257-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYZ	ENST00000340866.10 linkuse as main transcript	c.759A>G	p.Glu253Glu	synonymous_variant	8/9	1	NM_001889.4	ENSP00000339399.5		Q08257-1

Frequencies

GnomAD3 genomes

AF:

0.0299

AC:

4547

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0113

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0463

Gnomad OTH

AF:

0.0384

GnomAD3 exomes

AF:

0.0298

AC:

7469

AN:

250962

Hom.:

142

AF XY:

0.0300

AC XY:

4070

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.00911

Gnomad AMR exome

AF:

0.0223

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0166

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0412

AC:

60183

AN:

1460484

Hom.:

1391

Cov.:

AF XY:

0.0403

AC XY:

29314

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.00903

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.0346

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0480

Gnomad4 OTH exome

AF:

0.0373

GnomAD4 genome

AF:

0.0299

AC:

4547

AN:

152070

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

2058

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0113

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.0462

Gnomad4 OTH

AF:

0.0380

Alfa

AF:

0.0431

Hom.:

294

Bravo

AF:

0.0301

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0476

EpiControl

AF:

0.0445

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CRYZ-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2019

This 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

-0.49

CADD

Benign

6.6

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over