chr22-25227516-G-A

Position:

• chr22-25227516-G-A

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.174-337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 149,868 control chromosomes in the GnomAD database, including 4,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4294 hom., cov: 27)
• Consequence: CRYBB2 NM_000496.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.118

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=-0.88).
• BP6: Variant 22-25227516-G-A is Benign according to our data. Variant chr22-25227516-G-A is described in ClinVar as [Benign]. Clinvar id is 1270079.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-25227516-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBB2	NM_000496.3	c.174-337G>A		intron_variant		ENST00000398215.3	NP_000487.1
CRYBB2	XM_006724141.4	c.174-337G>A		intron_variant			XP_006724204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBB2	ENST00000398215.3	c.174-337G>A		intron_variant		1	NM_000496.3	ENSP00000381273	P1
CRYBB2	ENST00000651629.1	c.174-337G>A		intron_variant				ENSP00000498905	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32614 AN: 149750 Hom.: 4296 Cov.: 27

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 32621 AN: 149868 Hom.: 4294 Cov.: 27 AF XY: 0.212 AC XY: 15490 AN XY: 73022

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0842

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.182

Alfa AF: 0.0934 Hom.: 135

Bravo AF: 0.224

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 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.55

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: rs5760922; hg19: chr22-25623483;