2-208143069-A-G

Variant names:

• chr2-208143069-A-G
• rs796288
• NM_005210.4:c.253-156T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• early-onset anterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset lamellar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• total early-onset cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cataract 39 multiple types

  Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000295187 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005210.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYGB	NM_005210.4	MANE Select	c.253-156T>C		intron	N/A	NP_005201.2	P07316
	LOC100507443	NR_038437.1		n.221+5890A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYGB	ENST00000260988.5	TSL:1 MANE Select	c.253-156T>C		intron	N/A	ENSP00000260988.4	P07316
	ENSG00000295187	ENST00000728538.1		n.224+5890A>G		intron	N/A
	ENSG00000295187	ENST00000728539.1		n.241+5890A>G		intron	N/A

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

African (AFR) AF: 0.362 AC: 15031 AN: 41472

American (AMR) AF: 0.257 AC: 3923 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1575 AN: 5182

South Asian (SAS) AF: 0.203 AC: 979 AN: 4824

European-Finnish (FIN) AF: 0.261 AC: 2757 AN: 10576

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16871 AN: 67980

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.193 Hom.: 612

Bravo AF: 0.286

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs796288; hg19: chr2-209007793;