22-26625493-T-C

Variant names:

Variant summary

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

The NM_001886.3(CRYBA4):c.171T>C(p.Phe57Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,613,620 control chromosomes in the GnomAD database, including 598,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60204 hom., cov: 31)

Exomes 𝑓: 0.86 ( 538559 hom. )

Consequence

CRYBA4
NM_001886.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.258

Variant links:

Genes affected

CRYBA4 (HGNC:2396): (crystallin beta A4) 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, is part of a gene cluster with beta-B1, beta-B2, and beta-B3. [provided by RefSeq, Jul 2008]

CRYBA4 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 22-26625493-T-C is Benign according to our data. Variant chr22-26625493-T-C is described in ClinVar as [Benign]. Clinvar id is 258487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-26625493-T-C is described in Lovd as [Benign]. Variant chr22-26625493-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.258 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBA4	NM_001886.3 link	c.171T>C	p.Phe57Phe	synonymous_variant	Exon 4 of 6	ENST00000354760.4	NP_001877.1	P53673A0A097PIJ6
CRYBA4	XM_006724140.4 link	c.186T>C	p.Phe62Phe	synonymous_variant	Exon 6 of 8		XP_006724203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBA4	ENST00000354760.4 link	c.171T>C	p.Phe57Phe	synonymous_variant	Exon 4 of 6	1	NM_001886.3	ENSP00000346805.3		P53673
CRYBA4	ENST00000466315.1 link	n.68T>C		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

135059

AN:

152098

Hom.:

60146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.924

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.900

Gnomad ASJ

AF:

0.936

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.924

Gnomad FIN

AF:

0.925

Gnomad MID

AF:

0.886

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.908

GnomAD3 exomes

AF:

0.896

AC:

225031

AN:

251174

Hom.:

101162

AF XY:

0.894

AC XY:

121351

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.928

Gnomad AMR exome

AF:

0.943

Gnomad ASJ exome

AF:

0.931

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.923

Gnomad FIN exome

AF:

0.924

Gnomad NFE exome

AF:

0.846

Gnomad OTH exome

AF:

0.883

GnomAD4 exome

AF:

0.857

AC:

1252929

AN:

1461404

Hom.:

538559

Cov.:

AF XY:

0.859

AC XY:

624329

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.927

Gnomad4 AMR exome

AF:

0.939

Gnomad4 ASJ exome

AF:

0.933

Gnomad4 EAS exome

AF:

0.998

Gnomad4 SAS exome

AF:

0.921

Gnomad4 FIN exome

AF:

0.917

Gnomad4 NFE exome

AF:

0.836

Gnomad4 OTH exome

AF:

0.875

GnomAD4 genome

AF:

0.888

AC:

135177

AN:

152216

Hom.:

60204

Cov.:

AF XY:

0.892

AC XY:

66417

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.924

Gnomad4 AMR

AF:

0.900

Gnomad4 ASJ

AF:

0.936

Gnomad4 EAS

AF:

0.995

Gnomad4 SAS

AF:

0.924

Gnomad4 FIN

AF:

0.925

Gnomad4 NFE

AF:

0.845

Gnomad4 OTH

AF:

0.909

Alfa

AF:

0.856

Hom.:

19966

Bravo

AF:

0.889

Asia WGS

AF:

0.956

AC:

3323

AN:

3478

EpiCase

AF:

0.852

EpiControl

AF:

0.853

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 23

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.58

CADD

Benign

2.0

DANN

Benign

0.62

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