2-208146053-GCC-GC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005210.4(CRYGB):c.10-38delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,614,038 control chromosomes in the GnomAD database, including 16,328 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1835 hom., cov: 28)

Exomes 𝑓: 0.14 ( 14493 hom. )

Consequence

CRYGB
NM_005210.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: -0.606

Publications

5 publications found

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 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: Labcorp Genetics (formerly Invitae), G2P

CRYGB links:

ENSG00000295187 (HGNC:):

ENSG00000295187 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-208146053-GC-G is Benign according to our data. Variant chr2-208146053-GC-G is described in ClinVar as Benign. ClinVar VariationId is 41988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 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.10-38delG		intron	N/A	NP_005201.2	P07316
	LOC100507443	NR_038437.1		n.221+8879delC		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRYGB	ENST00000260988.5	TSL:1 MANE Select	c.10-38delG	intron	N/A	ENSP00000260988.4	P07316
ENSG00000295187	ENST00000728538.1		n.224+8875delC	intron	N/A
ENSG00000295187	ENST00000728539.1		n.241+8875delC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22920

AN:

152062

Hom.:

1835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0891

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.134

GnomAD2 exomes

AF:

0.136

AC:

34171

AN:

251308

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.0988

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.0924

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.139

AC:

203327

AN:

1461858

Hom.:

14493

Cov.:

AF XY:

0.140

AC XY:

101603

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.196

AC:

6565

AN:

33480

American (AMR)

AF:

0.101

AC:

4505

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

4219

AN:

26136

East Asian (EAS)

AF:

0.0863

AC:

3425

AN:

39700

South Asian (SAS)

AF:

0.156

AC:

13497

AN:

86258

European-Finnish (FIN)

AF:

0.136

AC:

7247

AN:

53420

Middle Eastern (MID)

AF:

0.147

AC:

847

AN:

5768

European-Non Finnish (NFE)

AF:

0.139

AC:

154421

AN:

1111976

Other (OTH)

AF:

0.142

AC:

8601

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

10690

21380

32071

42761

53451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5554

11108

16662

22216

27770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.151

AC:

22939

AN:

152180

Hom.:

1835

Cov.:

AF XY:

0.149

AC XY:

11092

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.196

AC:

8118

AN:

41496

American (AMR)

AF:

0.105

AC:

1610

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

546

AN:

3470

East Asian (EAS)

AF:

0.0883

AC:

458

AN:

5186

South Asian (SAS)

AF:

0.156

AC:

752

AN:

4832

European-Finnish (FIN)

AF:

0.134

AC:

1424

AN:

10590

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.139

AC:

9461

AN:

68008

Other (OTH)

AF:

0.133

AC:

281

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

999

1998

2998

3997

4996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.147

Hom.:

340

Bravo

AF:

0.148

Asia WGS

AF:

0.128

AC:

446

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 39 multiple types (4)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over