22-25221379-C-T

Variant names:

Variant summary

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

The NM_000496.3(CRYBB2):c.-26-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,502,510 control chromosomes in the GnomAD database, including 963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.018 ( 93 hom., cov: 32)

Exomes 𝑓: 0.020 ( 870 hom. )

Consequence

CRYBB2
NM_000496.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.211

Variant links:

Genes affected

CRYBB2 (HGNC:2398): (crystallin beta B2) 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, is part of a gene cluster with beta-A4, beta-B1, and beta-B3. A chain-terminating mutation was found to cause type 2 cerulean cataracts. [provided by RefSeq, Jul 2008]

CRYBB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 22-25221379-C-T is Benign according to our data. Variant chr22-25221379-C-T is described in ClinVar as [Benign]. Clinvar id is 1294002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB2	NM_000496.3 link	c.-26-25C>T		intron_variant	Intron 1 of 5	ENST00000398215.3	NP_000487.1	P43320R4UMM2
CRYBB2	XM_006724141.4 link	c.-26-25C>T		intron_variant	Intron 1 of 5		XP_006724204.1	P43320R4UMM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB2	ENST00000398215.3 link	c.-26-25C>T		intron_variant	Intron 1 of 5	1	NM_000496.3	ENSP00000381273.2		P43320
CRYBB2	ENST00000651629.1 link	c.-26-25C>T		intron_variant	Intron 1 of 5			ENSP00000498905.1		P43320

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2723

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0378

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0712

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.0350

AC:

8789

AN:

251100

Hom.:

412

AF XY:

0.0338

AC XY:

4590

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.0802

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.0598

Gnomad FIN exome

AF:

0.00439

Gnomad NFE exome

AF:

0.00968

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0198

AC:

26748

AN:

1350230

Hom.:

870

Cov.:

AF XY:

0.0205

AC XY:

13928

AN XY:

678094

show subpopulations

Gnomad4 AFR exome

AF:

0.00280

Gnomad4 AMR exome

AF:

0.0756

Gnomad4 ASJ exome

AF:

0.00428

Gnomad4 EAS exome

AF:

0.143

Gnomad4 SAS exome

AF:

0.0589

Gnomad4 FIN exome

AF:

0.00482

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.0229

GnomAD4 genome

AF:

0.0179

AC:

2720

AN:

152280

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1414

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00493

Gnomad4 AMR

AF:

0.0379

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0715

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0147

Hom.:

Bravo

AF:

0.0206

Asia WGS

AF:

0.0890

AC:

308

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.0

DANN

Benign

0.63

BranchPoint Hunter

4.0

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