17-29250316-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005208.5(CRYBA1):c.215+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,374,546 control chromosomes in the GnomAD database, including 822 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 170 hom., cov: 32)

Exomes 𝑓: 0.030 ( 652 hom. )

Consequence

CRYBA1
NM_005208.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.184

Publications

4 publications found

Variant links:

Genes affected

CRYBA1 (HGNC:2394): (crystallin beta A1) 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. Beta-crystallins, the most heterogeneous, differ by the presence of the C-terminal extension (present in the basic group, none in the acidic group). Beta-crystallins form aggregates of different sizes and are able to self-associate to form dimers or to form heterodimers with other beta-crystallins. This gene, a beta acidic group member, encodes two proteins (crystallin, beta A3 and crystallin, beta A1) from a single mRNA, the latter protein is 17 aa shorter than crystallin, beta A3 and is generated by use of an alternate translation initiation site. Deletion of exons 3 and 4 causes the autosomal dominant disease 'zonular cataract with sutural opacities'. [provided by RefSeq, Jul 2008]

CRYBA1 Gene-Disease associations (from GenCC):

cataract 10 multiple types
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
early-onset lamellar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset posterior polar cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
early-onset sutural cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CRYBA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-29250316-C-T is Benign according to our data. Variant chr17-29250316-C-T is described in ClinVar as [Benign]. Clinvar id is 259671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBA1	NM_005208.5 link	c.215+16C>T		intron_variant	Intron 3 of 5	ENST00000225387.8	NP_005199.2	P05813-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBA1	ENST00000225387.8 link	c.215+16C>T		intron_variant	Intron 3 of 5	1	NM_005208.5	ENSP00000225387.3		P05813-1
CRYBA1	ENST00000484605.1 link	n.203+16C>T		intron_variant	Intron 3 of 4	5		ENSP00000464368.1		J3QRT1

Frequencies

GnomAD3 genomes

AF:

0.0400

AC:

6075

AN:

152032

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0803

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0261

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0185

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0307

GnomAD2 exomes

AF:

0.0262

AC:

6590

AN:

251394

AF XY:

0.0254

show subpopulations

Gnomad AFR exome

AF:

0.0811

Gnomad AMR exome

AF:

0.0157

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.000435

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0289

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0298

AC:

36462

AN:

1222396

Hom.:

652

Cov.:

AF XY:

0.0293

AC XY:

18131

AN XY:

619716

show subpopulations

African (AFR)

AF:

0.0826

AC:

2405

AN:

29132

American (AMR)

AF:

0.0169

AC:

752

AN:

44410

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

354

AN:

24618

East Asian (EAS)

AF:

0.000207

AC:

AN:

38606

South Asian (SAS)

AF:

0.0218

AC:

1777

AN:

81564

European-Finnish (FIN)

AF:

0.0198

AC:

1055

AN:

53324

Middle Eastern (MID)

AF:

0.0352

AC:

182

AN:

5176

European-Non Finnish (NFE)

AF:

0.0320

AC:

28567

AN:

892988

Other (OTH)

AF:

0.0259

AC:

1362

AN:

52578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1576

3152

4727

6303

7879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1046

2092

3138

4184

5230

<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:

0.0400

AC:

6090

AN:

152150

Hom.:

170

Cov.:

AF XY:

0.0385

AC XY:

2861

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0805

AC:

3339

AN:

41474

American (AMR)

AF:

0.0261

AC:

399

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0187

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0186

AC:

197

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0283

AC:

1925

AN:

68004

Other (OTH)

AF:

0.0299

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

295

590

885

1180

1475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0330

Hom.:

Bravo

AF:

0.0412

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cataract 10 multiple types

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.2

(source)

DANN

Benign

0.62

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over