2-208143069-A-G

Position:

• chr2-208143069-A-G

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.253-156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,100 control chromosomes in the GnomAD database, including 6,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6214 hom., cov: 32)
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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=-0.83).
• BP6: Variant 2-208143069-A-G is Benign according to our data. Variant chr2-208143069-A-G is described in ClinVar as [Benign]. Clinvar id is 1282277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.253-156T>C		intron_variant		ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.259-156T>C		intron_variant			XP_016858891.1
LOC100507443	NR_038437.1	n.221+5890A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.253-156T>C		intron_variant		1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42351 AN: 151980 Hom.: 6195 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.279 AC: 42410 AN: 152100 Hom.: 6214 Cov.: 32 AF XY: 0.277 AC XY: 20611 AN XY: 74376

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.256

Alfa AF: 0.193 Hom.: 612

Bravo AF: 0.286

Asia WGS AF: 0.273 AC: 949 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

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.50

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: rs796288; hg19: chr2-209007793;