rs8080840

Variant names:

• chr17-29249001-G-A
• rs8080840
• NM_005208.5:c.32-141G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-29249001-G-A
• chr17-29249001-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005208.5(CRYBA1):​c.32-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 698,414 control chromosomes in the GnomAD database, including 6,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1386 hom., cov: 31)
  • Exomes 𝑓: 0.12 (5021 hom.)
• Consequence: CRYBA1 NM_005208.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.249
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-29249001-G-A is Benign according to our data. Variant chr17-29249001-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 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.32-141G>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.32-141G>A		intron	N/A	ENSP00000225387.3	P05813-1
	CRYBA1	ENST00000484605.1	TSL:5	n.20-141G>A		intron	N/A	ENSP00000464368.1	J3QRT1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19231 AN: 151888 Hom.: 1384 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0978

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.121 AC: 66323 AN: 546408 Hom.: 5021 AF XY: 0.122 AC XY: 36063 AN XY: 295054

African (AFR) AF: 0.153 AC: 2390 AN: 15626

American (AMR) AF: 0.122 AC: 4139 AN: 33886

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 1826 AN: 18640

East Asian (EAS) AF: 0.316 AC: 10132 AN: 32112

South Asian (SAS) AF: 0.164 AC: 10147 AN: 61702

European-Finnish (FIN) AF: 0.110 AC: 4556 AN: 41370

Middle Eastern (MID) AF: 0.0824 AC: 325 AN: 3946

European-Non Finnish (NFE) AF: 0.0949 AC: 29366 AN: 309308

Other (OTH) AF: 0.115 AC: 3442 AN: 29818

GnomAD4 genome AF: 0.127 AC: 19250 AN: 152006 Hom.: 1386 Cov.: 31 AF XY: 0.129 AC XY: 9546 AN XY: 74286

African (AFR) AF: 0.160 AC: 6643 AN: 41464

American (AMR) AF: 0.105 AC: 1599 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1533 AN: 5138

South Asian (SAS) AF: 0.169 AC: 814 AN: 4814

European-Finnish (FIN) AF: 0.117 AC: 1234 AN: 10586

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0977 AC: 6638 AN: 67940

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.109 Hom.: 140

Bravo AF: 0.129

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.67
PhyloP100		-0.25
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: rs8080840; hg19: chr17-27576019; COSMIC: COSV107307874;