chr2-208145688-CA-C

Position:

• chr2-208145688-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005210.4(CRYGB):​c.252+85delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 53,560 control chromosomes in the GnomAD database, including 278 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (278 hom., cov: 22)
  • Exomes 𝑓: 0.24 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.489

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 -10 ACMG points.

• BP6: Variant 2-208145688-CA-C is Benign according to our data. Variant chr2-208145688-CA-C is described in ClinVar as [Benign]. Clinvar id is 1257871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.252+85delT		intron_variant		ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.258+79delT		intron_variant			XP_016858891.1
LOC100507443	NR_038437.1	n.221+8532delA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.252+85delT		intron_variant		1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.232 AC: 12413 AN: 53568 Hom.: 276 Cov.: 22

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.231

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.244 AC: 283735 AN: 1161716 Hom.: 15 AF XY: 0.240 AC XY: 136372 AN XY: 567740

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.232 AC: 12420 AN: 53560 Hom.: 278 Cov.: 22 AF XY: 0.227 AC XY: 5650 AN XY: 24940

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0824

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.229

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

Aug 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs554918356; hg19: chr2-209010412;