chr17-29249894-CA-C

Variant names:

• chr17-29249894-CA-C
• rs79334339
• NM_005208.5:c.97-287delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005208.5(CRYBA1):​c.97-287delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,246 control chromosomes in the GnomAD database, including 1,069 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1069 hom., cov: 30)
• Consequence: CRYBA1 NM_005208.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.349
• Publications: 0 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), G2P, Ambry Genetics
• 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 -10 ACMG points.

• BP6: Variant 17-29249894-CA-C is Benign according to our data. Variant chr17-29249894-CA-C is described in ClinVar as [Benign]. Clinvar id is 1254997.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBA1	NM_005208.5	c.97-287delA		intron_variant	Intron 2 of 5	ENST00000225387.8	NP_005199.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBA1	ENST00000225387.8	c.97-287delA		intron_variant	Intron 2 of 5	1	NM_005208.5	ENSP00000225387.3
CRYBA1	ENST00000484605.1	n.85-287delA		intron_variant	Intron 2 of 4	5		ENSP00000464368.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16908 AN: 152128 Hom.: 1067 Cov.: 30

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0992

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.0915

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

GnomAD4 genome AF: 0.111 AC: 16918 AN: 152246 Hom.: 1069 Cov.: 30 AF XY: 0.113 AC XY: 8423 AN XY: 74452

African (AFR) AF: 0.107 AC: 4444 AN: 41546

American (AMR) AF: 0.0991 AC: 1516 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1542 AN: 5182

South Asian (SAS) AF: 0.169 AC: 815 AN: 4828

European-Finnish (FIN) AF: 0.116 AC: 1225 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0974 AC: 6623 AN: 68000

Other (OTH) AF: 0.0962 AC: 203 AN: 2110

Alfa AF: 0.0267 Hom.: 21

Bravo AF: 0.111

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79334339; hg19: chr17-27576912;