1-74724768-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001889.4(CRYZ):c.54G>A(p.Gly18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 1,611,268 control chromosomes in the GnomAD database, including 460,803 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 0.77 (44757 hom., cov: 32)
  • Exomes 𝑓: 0.75 (416046 hom.)
• Consequence: CRYZ NM_001889.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.223 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYZ	NM_001889.4	c.54G>A	p.Gly18=	synonymous_variant	2/9	ENST00000340866.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYZ	ENST00000340866.10	c.54G>A	p.Gly18=	synonymous_variant	2/9	1	NM_001889.4	P1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116392 AN: 151954 Hom.: 44707 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.733

GnomAD3 exomes AF: 0.755 AC: 188819 AN: 250040 Hom.: 71806 AF XY: 0.747 AC XY: 100895 AN XY: 135122

Gnomad AFR exome AF: 0.813

Gnomad AMR exome AF: 0.855

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.783

Gnomad SAS exome AF: 0.693

Gnomad FIN exome AF: 0.716

Gnomad NFE exome AF: 0.743

Gnomad OTH exome AF: 0.737

GnomAD4 exome AF: 0.754 AC: 1100107 AN: 1459196 Hom.: 416046 Cov.: 40 AF XY: 0.751 AC XY: 544994 AN XY: 725906

Gnomad4 AFR exome AF: 0.805

Gnomad4 AMR exome AF: 0.849

Gnomad4 ASJ exome AF: 0.686

Gnomad4 EAS exome AF: 0.805

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.755

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.766 AC: 116501 AN: 152072 Hom.: 44757 Cov.: 32 AF XY: 0.768 AC XY: 57045 AN XY: 74322

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.729

Alfa AF: 0.741 Hom.: 32240

Bravo AF: 0.775

Asia WGS AF: 0.722 AC: 2509 AN: 3478

EpiCase AF: 0.732

EpiControl AF: 0.726

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	8.0
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1051122; hg19: chr1-75190452;