rs2071862

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001886.3(CRYBA4):c.159-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,607,116 control chromosomes in the GnomAD database, including 20,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2078 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18888 hom. )

Consequence

CRYBA4
NM_001886.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0830

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-26625437-G-A is Benign according to our data. Variant chr22-26625437-G-A is described in ClinVar as [Benign]. Clinvar id is 677231.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBA4	NM_001886.3 linkuse as main transcript	c.159-44G>A		intron_variant		ENST00000354760.4
CRYBA4	XM_006724140.4 linkuse as main transcript	c.174-44G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBA4	ENST00000354760.4 linkuse as main transcript	c.159-44G>A		intron_variant		1	NM_001886.3	P1
CRYBA4	ENST00000466315.1 linkuse as main transcript	n.56-44G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23509

AN:

152008

Hom.:

2076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.152

GnomAD3 exomes

AF:

0.181

AC:

44975

AN:

248440

Hom.:

4720

AF XY:

0.181

AC XY:

24339

AN XY:

134348

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.206

Gnomad EAS exome

AF:

0.391

Gnomad SAS exome

AF:

0.239

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.152

AC:

221583

AN:

1454990

Hom.:

18888

Cov.:

AF XY:

0.155

AC XY:

112149

AN XY:

723622

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.208

Gnomad4 EAS exome

AF:

0.393

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.155

AC:

23512

AN:

152126

Hom.:

2078

Cov.:

AF XY:

0.157

AC XY:

11649

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.384

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.147

Hom.:

3681

Bravo

AF:

0.155

Asia WGS

AF:

0.241

AC:

836

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 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

-0.85

Cadd

Benign

5.4

Dann

Benign

0.72

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