22-25201744-C-CAT

Position:

• chr22-25201744-C-CAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004076.5(CRYBB3):​c.75+273_75+274insAT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (19196 hom., cov: 0)
• Consequence: CRYBB3 NM_004076.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.390

Genes affected

CRYBB3 (HGNC:2400): (crystallin beta B3) 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-B2. Mutations in this gene result in cataract congenital nuclear autosomal recessive type 2. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-25201744-C-CAT is Benign according to our data. Variant chr22-25201744-C-CAT is described in ClinVar as [Benign]. Clinvar id is 1247886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBB3	NM_004076.5	c.75+273_75+274insAT		intron_variant		ENST00000215855.7	NP_004067.1
CRYBB3	XM_047441147.1	c.75+273_75+274insAT		intron_variant			XP_047297103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBB3	ENST00000215855.7	c.75+273_75+274insAT		intron_variant		1	NM_004076.5	ENSP00000215855.2
CRYBB3	ENST00000404334.1	c.75+273_75+274insAT		intron_variant		3		ENSP00000386123.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74087 AN: 151628 Hom.: 19153 Cov.: 0

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.489 AC: 74186 AN: 151746 Hom.: 19196 Cov.: 0 AF XY: 0.486 AC XY: 36067 AN XY: 74158

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.585

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.504

Alfa AF: 0.436 Hom.: 1836

Bravo AF: 0.520

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

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3064261; hg19: chr22-25597711;