rs4276

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001886.3(CRYBA4):c.159-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,610,650 control chromosomes in the GnomAD database, including 208,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 26129 hom., cov: 31)

Exomes 𝑓: 0.50 ( 182723 hom. )

Consequence

CRYBA4
NM_001886.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.11

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-26625461-A-G is Benign according to our data. Variant chr22-26625461-A-G is described in ClinVar as [Benign]. Clinvar id is 258486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-26625461-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBA4	NM_001886.3 link	c.159-20A>G		intron_variant	Intron 3 of 5	ENST00000354760.4	NP_001877.1	P53673A0A097PIJ6
CRYBA4	XM_006724140.4 link	c.174-20A>G		intron_variant	Intron 5 of 7		XP_006724203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBA4	ENST00000354760.4 link	c.159-20A>G		intron_variant	Intron 3 of 5	1	NM_001886.3	ENSP00000346805.3		P53673
CRYBA4	ENST00000466315.1 link	n.56-20A>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87199

AN:

151882

Hom.:

26113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.747

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.649

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.545

GnomAD3 exomes

AF:

0.513

AC:

128364

AN:

250370

Hom.:

34348

AF XY:

0.509

AC XY:

68934

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.760

Gnomad AMR exome

AF:

0.378

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.654

Gnomad SAS exome

AF:

0.478

Gnomad FIN exome

AF:

0.588

Gnomad NFE exome

AF:

0.486

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.496

AC:

723674

AN:

1458650

Hom.:

182723

Cov.:

AF XY:

0.496

AC XY:

359598

AN XY:

725682

show subpopulations

Gnomad4 AFR exome

AF:

0.760

Gnomad4 AMR exome

AF:

0.386

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.651

Gnomad4 SAS exome

AF:

0.477

Gnomad4 FIN exome

AF:

0.585

Gnomad4 NFE exome

AF:

0.481

Gnomad4 OTH exome

AF:

0.524

GnomAD4 genome

AF:

0.574

AC:

87259

AN:

152000

Hom.:

26129

Cov.:

AF XY:

0.576

AC XY:

42766

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.478

Gnomad4 ASJ

AF:

0.572

Gnomad4 EAS

AF:

0.649

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.544

Alfa

AF:

0.510

Hom.:

10517

Bravo

AF:

0.570

Asia WGS

AF:

0.550

AC:

1911

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cataract 23

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jun 19, 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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.89

CADD

Benign

0.045

DANN

Benign

0.47

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