XM_006724140.4:c.4-1114C>G

Variant names:

• chr22-26621471-C-G
• rs5997109
• XM_006724140.4:c.4-1114C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

CRYBA4 Gene-Disease associations (from GenCC):

• cataract 23

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• cataract - microcornea syndrome

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.342 AC: 14175 AN: 41460

American (AMR) AF: 0.489 AC: 7480 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1647 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2367 AN: 5158

South Asian (SAS) AF: 0.506 AC: 2434 AN: 4814

European-Finnish (FIN) AF: 0.460 AC: 4870 AN: 10578

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27145 AN: 67968

Other (OTH) AF: 0.464 AC: 978 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.50
PhyloP100		0.34
PromoterAI		-0.0060	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5997109; hg19: chr22-27017435;