chr2-208146053-GC-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: -0.606

Variant links:

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]

CRYGB links:

LOC100507443 (HGNC:):

LOC100507443 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
CRYGB	NM_005210.4 link	c.10-38delG	intron_variant	Intron 1 of 2	ENST00000260988.5	NP_005201.2	P07316
CRYGB	XM_017003402.2 link	c.10-38delG	intron_variant	Intron 1 of 2		XP_016858891.1
LOC100507443	NR_038437.1 link	n.221+8879delC	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5 link	c.10-38delG		intron_variant	Intron 1 of 2	1	NM_005210.4	ENSP00000260988.4		P07316

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22920

AN:

152062

Hom.:

1835

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.140

AC XY:

101603

AN XY:

727232

show subpopulations

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.:

AF XY:

0.149

AC XY:

11092

AN XY:

74422

show subpopulations

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:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 39 multiple types

Pathogenic:1Benign:3

Jan 01, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

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

Oct 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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