chr22-25201744-C-CAT

Variant names:

• chr22-25201744-C-CAT
• rs3064261
• NM_004076.5:c.75+273_75+274insAT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

CRYBB3 Gene-Disease associations (from GenCC):

• cataract 22 multiple types

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• early-onset anterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset nuclear cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset non-syndromic cataract

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004076.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBB3	NM_004076.5	MANE Select	c.75+273_75+274insAT		intron	N/A	NP_004067.1	P26998

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBB3	ENST00000215855.7	TSL:1 MANE Select	c.75+273_75+274insAT		intron	N/A	ENSP00000215855.2	P26998
	CRYBB3	ENST00000404334.1	TSL:3	c.75+273_75+274insAT		intron	N/A	ENSP00000386123.1	B1AHR5

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

African (AFR) AF: 0.649 AC: 26841 AN: 41352

American (AMR) AF: 0.528 AC: 8063 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1687 AN: 3462

East Asian (EAS) AF: 0.585 AC: 2997 AN: 5122

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4822

European-Finnish (FIN) AF: 0.361 AC: 3806 AN: 10534

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27788 AN: 67870

Other (OTH) AF: 0.504 AC: 1065 AN: 2114

Alfa AF: 0.436 Hom.: 1836

Bravo AF: 0.520

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.39
Mutation Taster		=18/82	disease causing

Splicing

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

Other links and lift over

dbSNP: rs3064261; hg19: chr22-25597711;