rs8080081

Positions:

• chr17-29252605-C-A
• chr17-29252605-C-T

Variant summary

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

The NM_005208.5(CRYBA1):​c.357+400C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 120,848 control chromosomes in the GnomAD database, including 3,617 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 0.27 (3617 hom., cov: 29)
• Consequence: CRYBA1 NM_005208.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

Genes affected

CRYBA1 (HGNC:2394): (crystallin beta A1) 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, encodes two proteins (crystallin, beta A3 and crystallin, beta A1) from a single mRNA, the latter protein is 17 aa shorter than crystallin, beta A3 and is generated by use of an alternate translation initiation site. Deletion of exons 3 and 4 causes the autosomal dominant disease 'zonular cataract with sutural opacities'. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBA1	NM_005208.5	c.357+400C>A		intron_variant		ENST00000225387.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBA1	ENST00000225387.8	c.357+400C>A		intron_variant		1	NM_005208.5	P1
CRYBA1	ENST00000484605.1	c.206-1035C>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 33180 AN: 120728 Hom.: 3610 Cov.: 29

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.275 AC: 33227 AN: 120848 Hom.: 3617 Cov.: 29 AF XY: 0.276 AC XY: 16434 AN XY: 59446

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.242

Alfa AF: 0.101 Hom.: 171

Bravo AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8080081; hg19: chr17-27579623;