1-74724768-C-T

Variant names:

• chr1-74724768-C-T
• rs1051122
• NM_001889.4:c.54G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001889.4(CRYZ):​c.54G>A​(p.Gly18Gly) 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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYZ	NM_001889.4	MANE Select	c.54G>A	p.Gly18Gly	synonymous	Exon 2 of 9	NP_001880.2
	CRYZ	NM_001130042.2		c.54G>A	p.Gly18Gly	synonymous	Exon 3 of 10	NP_001123514.1	Q08257-1
	CRYZ	NM_001130043.2		c.54G>A	p.Gly18Gly	synonymous	Exon 2 of 8	NP_001123515.1	Q08257-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYZ	ENST00000340866.10	TSL:1 MANE Select	c.54G>A	p.Gly18Gly	synonymous	Exon 2 of 9	ENSP00000339399.5	Q08257-1
	CRYZ	ENST00000370871.7	TSL:1	c.54G>A	p.Gly18Gly	synonymous	Exon 2 of 8	ENSP00000359908.3	Q08257-3
	CRYZ	ENST00000370872.7	TSL:1	c.-136-1498G>A		intron	N/A	ENSP00000359909.3	Q08257-2

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

GnomAD2 exomes AF: 0.755 AC: 188819 AN: 250040 AF XY: 0.747

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 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

African (AFR) AF: 0.805 AC: 26874 AN: 33398

American (AMR) AF: 0.849 AC: 37768 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 17897 AN: 26084

East Asian (EAS) AF: 0.805 AC: 31848 AN: 39580

South Asian (SAS) AF: 0.697 AC: 59908 AN: 85910

European-Finnish (FIN) AF: 0.716 AC: 38206 AN: 53388

Middle Eastern (MID) AF: 0.690 AC: 3971 AN: 5756

European-Non Finnish (NFE) AF: 0.755 AC: 838721 AN: 1110268

Other (OTH) AF: 0.745 AC: 44914 AN: 60312

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

African (AFR) AF: 0.811 AC: 33645 AN: 41482

American (AMR) AF: 0.805 AC: 12288 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2362 AN: 3466

East Asian (EAS) AF: 0.785 AC: 4054 AN: 5166

South Asian (SAS) AF: 0.711 AC: 3426 AN: 4818

European-Finnish (FIN) AF: 0.723 AC: 7636 AN: 10566

Middle Eastern (MID) AF: 0.693 AC: 201 AN: 290

European-Non Finnish (NFE) AF: 0.744 AC: 50608 AN: 67988

Other (OTH) AF: 0.729 AC: 1542 AN: 2116

Alfa AF: 0.748 Hom.: 56987

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.0
DANN	Benign	0.63
PhyloP100		0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Other links and lift over

dbSNP: rs1051122; hg19: chr1-75190452; COSMIC: COSV108165568;