rs2239832

Variant names:

• chr22-26625972-A-G
• rs2239832
• NM_001886.3:c.300+350A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-26625972-A-G
• chr22-26625972-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001886.3(CRYBA4):​c.300+350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,654 control chromosomes in the GnomAD database, including 9,692 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 0.32 (9692 hom., cov: 31)
• Consequence: CRYBA4 NM_001886.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 3 publications found

Genes affected

CRYBA4 (HGNC:2396): (crystallin beta A4) 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, is part of a gene cluster with beta-B1, beta-B2, and beta-B3. [provided by RefSeq, Jul 2008]

CRYBA4 Gene-Disease associations (from GenCC):

• cataract 23

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• cataract - microcornea syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• early-onset lamellar 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBA4	NM_001886.3	c.300+350A>G		intron_variant	Intron 4 of 5	ENST00000354760.4	NP_001877.1
CRYBA4	XM_006724140.4	c.315+350A>G		intron_variant	Intron 6 of 7		XP_006724203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBA4	ENST00000354760.4	c.300+350A>G		intron_variant	Intron 4 of 5	1	NM_001886.3	ENSP00000346805.3
CRYBA4	ENST00000466315.1	n.197+350A>G		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48400 AN: 151536 Hom.: 9675 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.320 AC: 48462 AN: 151654 Hom.: 9692 Cov.: 31 AF XY: 0.322 AC XY: 23826 AN XY: 74072

African (AFR) AF: 0.558 AC: 23066 AN: 41322

American (AMR) AF: 0.269 AC: 4109 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 979 AN: 3468

East Asian (EAS) AF: 0.488 AC: 2510 AN: 5148

South Asian (SAS) AF: 0.328 AC: 1574 AN: 4804

European-Finnish (FIN) AF: 0.249 AC: 2615 AN: 10484

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12704 AN: 67868

Other (OTH) AF: 0.304 AC: 640 AN: 2106

Alfa AF: 0.240 Hom.: 1098

Bravo AF: 0.329

Asia WGS AF: 0.397 AC: 1380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.48
PhyloP100		0.20
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: rs2239832; hg19: chr22-27021936;