rs8080081

Variant names:

• chr17-29252605-C-A
• rs8080081
• NM_005208.5:c.357+400C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

CRYBA1 Gene-Disease associations (from GenCC):

• cataract 10 multiple types

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• early-onset lamellar cataract

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset sutural 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005208.5. 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
	CRYBA1	NM_005208.5	MANE Select	c.357+400C>A		intron	N/A	NP_005199.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBA1	ENST00000225387.8	TSL:1 MANE Select	c.357+400C>A		intron	N/A	ENSP00000225387.3	P05813-1
	CRYBA1	ENST00000484605.1	TSL:5	n.204-1035C>A		intron	N/A	ENSP00000464368.1	J3QRT1

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

African (AFR) AF: 0.384 AC: 13281 AN: 34592

American (AMR) AF: 0.220 AC: 2527 AN: 11490

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 500 AN: 2678

East Asian (EAS) AF: 0.375 AC: 1680 AN: 4478

South Asian (SAS) AF: 0.394 AC: 1635 AN: 4148

European-Finnish (FIN) AF: 0.219 AC: 1917 AN: 8754

Middle Eastern (MID) AF: 0.165 AC: 34 AN: 206

European-Non Finnish (NFE) AF: 0.212 AC: 11051 AN: 52112

Other (OTH) AF: 0.242 AC: 402 AN: 1660

Alfa AF: 0.112 Hom.: 207

Bravo AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.40
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8080081; hg19: chr17-27579623;