rs1047790

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005208.5(CRYBA1):c.456C>T(p.Gly152Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,442 control chromosomes in the GnomAD database, including 33,265 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4298 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28967 hom. )

Consequence

CRYBA1
NM_005208.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.811

Publications

22 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), Ambry Genetics, G2P
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 17-29253738-C-T is Benign according to our data. Variant chr17-29253738-C-T is described in ClinVar as Benign. ClinVar VariationId is 259672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.811 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005208.5. 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
	CRYBA1	NM_005208.5	MANE Select	c.456C>T	p.Gly152Gly	synonymous	Exon 5 of 6	NP_005199.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRYBA1	ENST00000225387.8	TSL:1 MANE Select	c.456C>T	p.Gly152Gly	synonymous	Exon 5 of 6	ENSP00000225387.3	P05813-1
CRYBA1	ENST00000484605.1	TSL:5	n.*77C>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000464368.1	J3QRT1
CRYBA1	ENST00000484605.1	TSL:5	n.*77C>T		3_prime_UTR	Exon 4 of 5	ENSP00000464368.1	J3QRT1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34102

AN:

151948

Hom.:

4290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.332

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.213

AC:

53634

AN:

251434

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.340

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.165

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.190

AC:

278006

AN:

1461374

Hom.:

28967

Cov.:

AF XY:

0.193

AC XY:

140604

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.332

AC:

11115

AN:

33470

American (AMR)

AF:

0.163

AC:

7301

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.142

AC:

3709

AN:

26134

East Asian (EAS)

AF:

0.348

AC:

13797

AN:

39690

South Asian (SAS)

AF:

0.347

AC:

29885

AN:

86234

European-Finnish (FIN)

AF:

0.177

AC:

9458

AN:

53420

Middle Eastern (MID)

AF:

0.169

AC:

977

AN:

5766

European-Non Finnish (NFE)

AF:

0.171

AC:

190156

AN:

1111558

Other (OTH)

AF:

0.192

AC:

11608

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

11256

22512

33768

45024

56280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7148

14296

21444

28592

35740

<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:

0.225

AC:

34152

AN:

152068

Hom.:

4298

Cov.:

AF XY:

0.227

AC XY:

16890

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.333

AC:

13788

AN:

41444

American (AMR)

AF:

0.169

AC:

2589

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

513

AN:

3470

East Asian (EAS)

AF:

0.332

AC:

1714

AN:

5164

South Asian (SAS)

AF:

0.350

AC:

1686

AN:

4820

European-Finnish (FIN)

AF:

0.183

AC:

1932

AN:

10574

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11275

AN:

67990

Other (OTH)

AF:

0.197

AC:

415

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1277

2554

3831

5108

6385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.177

Hom.:

4683

Bravo

AF:

0.225

Asia WGS

AF:

0.361

AC:

1256

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.157

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Cataract 10 multiple types (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.2

(source)

DANN

Benign

0.86

PhyloP100

0.81

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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