22-26621471-C-G

Position:

• chr22-26621471-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_006724140.4(CRYBA4):​c.4-1114C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,048 control chromosomes in the GnomAD database, including 12,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (12781 hom., cov: 32)
• Consequence: CRYBA4 XM_006724140.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

Genes affected

CRYBA4 (HGNC:2396): (crystallin beta A4) 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 acidic group member, is part of a gene cluster with beta-B1, beta-B2, and beta-B3. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBA4	XM_006724140.4	c.4-1114C>G		intron_variant			XP_006724203.1
		n.26621471C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61428 AN: 151930 Hom.: 12760 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.404 AC: 61501 AN: 152048 Hom.: 12781 Cov.: 32 AF XY: 0.410 AC XY: 30476 AN XY: 74340

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.464

Alfa AF: 0.260 Hom.: 606

Bravo AF: 0.408

Asia WGS AF: 0.543 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5997109; hg19: chr22-27017435;