chr17-29252605-C-T

Position:

• chr17-29252605-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005208.5(CRYBA1):​c.357+400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 116,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0054 (0 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=-0.78).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00536 (625/116556) while in subpopulation AFR AF= 0.00619 (207/33456). AF 95% confidence interval is 0.0055. There are 0 homozygotes in gnomad4. There are 290 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 625 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00536 AC: 624 AN: 116440 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00621

Gnomad AMI AF: 0.00573

Gnomad AMR AF: 0.00619

Gnomad ASJ AF: 0.00511

Gnomad EAS AF: 0.00480

Gnomad SAS AF: 0.00320

Gnomad FIN AF: 0.00219

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.00702

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

GnomAD4 genome AF: 0.00536 AC: 625 AN: 116556 Hom.: 0 Cov.: 29 AF XY: 0.00504 AC XY: 290 AN XY: 57558

Gnomad4 AFR AF: 0.00619

Gnomad4 AMR AF: 0.00619

Gnomad4 ASJ AF: 0.00511

Gnomad4 EAS AF: 0.00481

Gnomad4 SAS AF: 0.00321

Gnomad4 FIN AF: 0.00219

Gnomad4 NFE AF: 0.00532

Gnomad4 OTH AF: 0.00694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.4
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;