rs739315

chr22-25221635-A-Gchr22-25221635-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000496.3(CRYBB2):c.54+152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 645,064 control chromosomes in the GnomAD database, including 59,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11870 hom., cov: 33)
  • Exomes 𝑓: 0.44 (47627 hom.)
• Consequence: CRYBB2 NM_000496.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.79

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-25221635-A-G is Benign according to our data. Variant chr22-25221635-A-G is described in ClinVar as [Benign]. Clinvar id is 1258808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBB2	NM_000496.3	c.54+152A>G		intron_variant		ENST00000398215.3
CRYBB2	XM_006724141.4	c.54+152A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBB2	ENST00000398215.3	c.54+152A>G		intron_variant		1	NM_000496.3	P1
CRYBB2	ENST00000651629.1	c.54+152A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59013 AN: 151894 Hom.: 11862 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.435 AC: 214661 AN: 493050 Hom.: 47627 AF XY: 0.437 AC XY: 114554 AN XY: 262240

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.454

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.388 AC: 59055 AN: 152014 Hom.: 11870 Cov.: 33 AF XY: 0.392 AC XY: 29146 AN XY: 74294

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.455

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.425

Alfa AF: 0.420 Hom.: 11327

Bravo AF: 0.380

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.11
Dann	Benign	0.58

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

Other links and lift over

dbSNP: rs739315; hg19: chr22-25617602;