2-208146053-GCC-GC

Position:

• chr2-208146053-GCC-GC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005210.4(CRYGB):​c.10-38delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,614,038 control chromosomes in the GnomAD database, including 16,328 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1835 hom., cov: 28)
  • Exomes 𝑓: 0.14 (14493 hom.)
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:4
• Conservation: PhyloP100: -0.606

Genes affected

CRYGB (HGNC:2409): (crystallin gamma B) 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. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups. Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

LOC100507443 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-208146053-GC-G is Benign according to our data. Variant chr2-208146053-GC-G is described in ClinVar as [Benign]. Clinvar id is 41988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.10-38delG		intron_variant		ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.10-38delG		intron_variant			XP_016858891.1
LOC100507443	NR_038437.1	n.221+8879delC		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.10-38delG		intron_variant		1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22920 AN: 152062 Hom.: 1835 Cov.: 28

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.136 AC: 34171 AN: 251308 Hom.: 2407 AF XY: 0.136 AC XY: 18524 AN XY: 135828

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.0988

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.0924

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.139 AC: 203327 AN: 1461858 Hom.: 14493 Cov.: 35 AF XY: 0.140 AC XY: 101603 AN XY: 727232

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.0863

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.151 AC: 22939 AN: 152180 Hom.: 1835 Cov.: 28 AF XY: 0.149 AC XY: 11092 AN XY: 74422

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0883

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.133

Alfa AF: 0.147 Hom.: 340

Bravo AF: 0.148

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cataract 39 multiple types Pathogenic:1 Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 29, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jan 01, 2012	- -
Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NG_028158.1(NM_005210.3):c.10-38delG in the CRYGB gene has an allele frequency of 0.192 in African subpopulation in the gnomAD database, including 2819 homozygous. This variant was reported as g.67delG in a pedigree, which detected in congenital cataracts patients and a normal sibling (PMID: 23288985). This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 15, 2018

This variant is associated with the following publications: (PMID: 23288985) -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3214759; hg19: chr2-209010777;