Variant chr22-26601766-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001887.4(CRYBB1):c.575+113T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,544,878 control chromosomes in the GnomAD database, including 36,791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 3118 hom., cov: 31)

Exomes 𝑓: 0.21 ( 33673 hom. )

Consequence

CRYBB1
NM_001887.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.885

Variant links:

Genes affected

CRYBB1 (HGNC:2397): (crystallin beta B1) 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 basic group member, undergoes extensive cleavage at its N-terminal extension during lens maturation. It is also a member of a gene cluster with beta-A4, beta-B2, and beta-B3. [provided by RefSeq, Jul 2008]

CRYBB1 links:

(HGNC:):

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=-0.86).

BP6

Variant 22-26601766-A-T is Benign according to our data. Variant chr22-26601766-A-T is described in ClinVar as [Benign]. Clinvar id is 1273779.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CRYBB1	NM_001887.4 linkuse as main transcript	c.575+113T>A	intron_variant	ENST00000647684.1	NP_001878.1
CRYBA4	XM_006724140.4 linkuse as main transcript	c.-239+4683A>T	intron_variant		XP_006724203.1
CRYBB1	XM_011529899.4 linkuse as main transcript	c.575+113T>A	intron_variant		XP_011528201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBB1	ENST00000647684.1 linkuse as main transcript	c.575+113T>A		intron_variant			NM_001887.4	ENSP00000497249	P1
	ENST00000668614.1 linkuse as main transcript	n.56+4683A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26698

AN:

151422

Hom.:

3097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0552

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.208

AC:

289793

AN:

1393338

Hom.:

33673

AF XY:

0.212

AC XY:

146893

AN XY:

692664

show subpopulations

Gnomad4 AFR exome

AF:

0.0475

Gnomad4 AMR exome

AF:

0.413

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.176

AC:

26736

AN:

151540

Hom.:

3118

Cov.:

AF XY:

0.183

AC XY:

13591

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.0551

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.377

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.172

Hom.:

312

Bravo

AF:

0.178

Asia WGS

AF:

0.427

AC:

1482

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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.81

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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