Variant 22-26623190-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001886.3(CRYBA4):c.40-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,527,618 control chromosomes in the GnomAD database, including 1,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 202 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1222 hom. )

Consequence

CRYBA4
NM_001886.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.49

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 22-26623190-G-A is Benign according to our data. Variant chr22-26623190-G-A is described in ClinVar as [Benign]. Clinvar id is 1221696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBA4	NM_001886.3 linkuse as main transcript	c.40-44G>A		intron_variant		ENST00000354760.4	NP_001877.1
CRYBA4	XM_006724140.4 linkuse as main transcript	c.55-44G>A		intron_variant			XP_006724203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBA4	ENST00000354760.4 linkuse as main transcript	c.40-44G>A		intron_variant		1	NM_001886.3	ENSP00000346805	P1
CRYBA4	ENST00000466315.1 linkuse as main transcript	n.55+555G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6830

AN:

152142

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0443

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0366

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0954

Gnomad SAS

AF:

0.0680

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0475

GnomAD3 exomes

AF:

0.0476

AC:

11654

AN:

244618

Hom.:

365

AF XY:

0.0481

AC XY:

6400

AN XY:

133144

show subpopulations

Gnomad AFR exome

AF:

0.0462

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0445

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.0617

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.0341

Gnomad OTH exome

AF:

0.0460

GnomAD4 exome

AF:

0.0356

AC:

48947

AN:

1375360

Hom.:

1222

Cov.:

AF XY:

0.0365

AC XY:

25165

AN XY:

689094

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.0252

Gnomad4 ASJ exome

AF:

0.0464

Gnomad4 EAS exome

AF:

0.0792

Gnomad4 SAS exome

AF:

0.0584

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0282

Gnomad4 OTH exome

AF:

0.0448

GnomAD4 genome

AF:

0.0449

AC:

6843

AN:

152258

Hom.:

202

Cov.:

AF XY:

0.0485

AC XY:

3607

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0445

Gnomad4 AMR

AF:

0.0365

Gnomad4 ASJ

AF:

0.0530

Gnomad4 EAS

AF:

0.0947

Gnomad4 SAS

AF:

0.0683

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0508

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0383

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.19

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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