rs2071859

chr22-26608336-G-T

Variant summary

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

The NM_001887.4(CRYBB1):c.300-315C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,174 control chromosomes in the GnomAD database, including 1,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1754 hom., cov: 33)
• Consequence: CRYBB1 NM_001887.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.352

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-26608336-G-T is Benign according to our data. Variant chr22-26608336-G-T is described in ClinVar as [Benign]. Clinvar id is 1250226.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBB1	NM_001887.4	c.300-315C>A		intron_variant		ENST00000647684.1
CRYBA4	XM_006724140.4	c.3+274G>T		intron_variant
CRYBB1	XM_011529899.4	c.300-315C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBB1	ENST00000647684.1	c.300-315C>A		intron_variant			NM_001887.4	P1
	ENST00000668614.1	n.297+274G>T		intron_variant, non_coding_transcript_variant
CRYBB1	ENST00000647569.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21739 AN: 152056 Hom.: 1751 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.143 AC: 21744 AN: 152174 Hom.: 1754 Cov.: 33 AF XY: 0.144 AC XY: 10710 AN XY: 74376

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.137

Alfa AF: 0.138 Hom.: 233

Bravo AF: 0.145

Asia WGS AF: 0.214 AC: 741 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

Aug 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.63
Dann	Benign	0.59

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: rs2071859; hg19: chr22-27004300;