Variant 2-208143062-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005210.4(CRYGB):c.253-149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 704,548 control chromosomes in the GnomAD database, including 73,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 13751 hom., cov: 32)

Exomes 𝑓: 0.45 ( 59416 hom. )

Consequence

CRYGB
NM_005210.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.382

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-208143062-A-G is Benign according to our data. Variant chr2-208143062-A-G is described in ClinVar as [Benign]. Clinvar id is 1183509.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CRYGB	NM_005210.4 linkuse as main transcript	c.253-149T>C	intron_variant	ENST00000260988.5	NP_005201.2	P07316
CRYGB	XM_017003402.2 linkuse as main transcript	c.259-149T>C	intron_variant		XP_016858891.1
LOC100507443	NR_038437.1 linkuse as main transcript	n.221+5883A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5 linkuse as main transcript	c.253-149T>C		intron_variant		1	NM_005210.4	ENSP00000260988.4		P07316

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63150

AN:

151998

Hom.:

13739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.579

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.451

AC:

248922

AN:

552432

Hom.:

59416

AF XY:

0.455

AC XY:

129271

AN XY:

284318

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.582

Gnomad4 EAS exome

AF:

0.211

Gnomad4 SAS exome

AF:

0.485

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.475

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.415

AC:

63190

AN:

152116

Hom.:

13751

Cov.:

AF XY:

0.415

AC XY:

30827

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.579

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.504

Gnomad4 FIN

AF:

0.451

Gnomad4 NFE

AF:

0.489

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.447

Hom.:

1912

Bravo

AF:

0.397

Asia WGS

AF:

0.356

AC:

1238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.61

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

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