2-208145545-T-C

Position:

• chr2-208145545-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005210.4(CRYGB):​c.252+229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 151,608 control chromosomes in the GnomAD database, including 65,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.93 (65648 hom., cov: 27)
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 2-208145545-T-C is Benign according to our data. Variant chr2-208145545-T-C is described in ClinVar as [Benign]. Clinvar id is 1237178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.252+229A>G		intron_variant		ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.258+223A>G		intron_variant			XP_016858891.1
LOC100507443	NR_038437.1	n.221+8366T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.252+229A>G		intron_variant		1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140319 AN: 151488 Hom.: 65590 Cov.: 27

Gnomad AFR AF: 0.950

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.919

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.926 AC: 140441 AN: 151608 Hom.: 65648 Cov.: 27 AF XY: 0.920 AC XY: 68142 AN XY: 74040

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.962

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.919

Alfa AF: 0.946 Hom.: 3226

Bravo AF: 0.916

Asia WGS AF: 0.683 AC: 2377 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-1.1
CADD	Benign	0.74
DANN	Benign	0.17

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: rs796282; hg19: chr2-209010269;