17-29253738-C-T

Position:

chr17-29253738-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005208.5(CRYBA1):c.456C>T(p.Gly152=) 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:5

Conservation

PhyloP100: 0.811

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-29253738-C-T is described in Lovd as [Benign]. Variant chr17-29253738-C-T is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBA1	NM_005208.5 linkuse as main transcript	c.456C>T	p.Gly152=	synonymous_variant	5/6	ENST00000225387.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBA1	ENST00000225387.8 linkuse as main transcript	c.456C>T	p.Gly152=	synonymous_variant	5/6	1	NM_005208.5	P1	P05813-1
CRYBA1	ENST00000484605.1 linkuse as main transcript	c.*77C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	5

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

GnomAD3 exomes

AF:

0.213

AC:

53634

AN:

251434

Hom.:

6651

AF XY:

0.217

AC XY:

29468

AN XY:

135898

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 SAS exome

AF:

0.350

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

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.225

AC:

34152

AN:

152068

Hom.:

4298

Cov.:

AF XY:

0.227

AC XY:

16890

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.332

Gnomad4 SAS

AF:

0.350

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.167

Hom.:

2968

Bravo

AF:

0.225

Asia WGS

AF:

0.361

AC:

1256

AN:

3478

EpiCase

AF:

0.151

EpiControl

AF:

0.157

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Cataract 10 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 02, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.2

DANN

Benign

0.86

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