rs76323117

Positions:

chr2-208145851-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005210.4(CRYGB):c.175C>T(p.Arg59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,102 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 14 hom., cov: 31)

Exomes 𝑓: 0.00072 ( 9 hom. )

Consequence

CRYGB
NM_005210.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.03

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012019426).

BP6

Variant 2-208145851-G-A is Benign according to our data. Variant chr2-208145851-G-A is described in ClinVar as [Benign]. Clinvar id is 474170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0069 (1050/152234) while in subpopulation AFR AF= 0.0242 (1006/41538). AF 95% confidence interval is 0.023. There are 14 homozygotes in gnomad4. There are 527 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1050 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYGB	NM_005210.4 linkuse as main transcript	c.175C>T	p.Arg59Trp	missense_variant	2/3	ENST00000260988.5	NP_005201.2	P07316
CRYGB	XM_017003402.2 linkuse as main transcript	c.175C>T	p.Arg59Trp	missense_variant	2/3		XP_016858891.1
LOC100507443	NR_038437.1 linkuse as main transcript	n.221+8672G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5 linkuse as main transcript	c.175C>T	p.Arg59Trp	missense_variant	2/3	1	NM_005210.4	ENSP00000260988.4		P07316

Frequencies

GnomAD3 genomes

AF:

0.00690

AC:

1050

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00172

AC:

432

AN:

251334

Hom.:

AF XY:

0.00124

AC XY:

169

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0238

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000722

AC:

1055

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000602

AC XY:

438

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0253

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.00197

GnomAD4 genome

AF:

0.00690

AC:

1050

AN:

152234

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00756

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cataract 39 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.071

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.013

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.41

Sift

Benign

0.16

Sift4G

Benign

0.084

Polyphen

1.0

Vest4

0.59

MVP

0.84

MPC

0.14

ClinPred

0.053

GERP RS

2.9

Varity_R

0.41

gMVP

0.40

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