rs143137736

Positions:

chr22-26628311-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001886.3(CRYBA4):c.324A>T(p.Thr108Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,978 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 53 hom. )

Consequence

CRYBA4
NM_001886.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.253

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:

CRYBA4 (HGNC:):

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=-0.56).

BP6

Variant 22-26628311-A-T is Benign according to our data. Variant chr22-26628311-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 474086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.253 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00226 (344/152112) while in subpopulation AMR AF= 0.0189 (289/15288). AF 95% confidence interval is 0.0171. There are 2 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 344 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBA4	NM_001886.3 linkuse as main transcript	c.324A>T	p.Thr108Thr	synonymous_variant	5/6	ENST00000354760.4	NP_001877.1	P53673A0A097PIJ6
CRYBA4	XM_006724140.4 linkuse as main transcript	c.339A>T	p.Thr113Thr	synonymous_variant	7/8		XP_006724203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBA4	ENST00000354760.4 linkuse as main transcript	c.324A>T	p.Thr108Thr	synonymous_variant	5/6	1	NM_001886.3	ENSP00000346805.3		P53673
CRYBA4	ENST00000466315.1 linkuse as main transcript	n.221A>T		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

340

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000991

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00616

AC:

1550

AN:

251492

Hom.:

AF XY:

0.00473

AC XY:

643

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.0438

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00139

AC:

2034

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

879

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0433

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152112

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000988

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00503

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cataract 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

CRYBA4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.2

DANN

Benign

0.65

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