chr22-26623213-CT-C

Position:

• chr22-26623213-CT-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001886.3(CRYBA4):​c.40-11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,160,634 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRYBA4 NM_001886.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.318

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 22-26623213-CT-C is Benign according to our data. Variant chr22-26623213-CT-C is described in ClinVar as [Benign]. Clinvar id is 2892141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 3276 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBA4	NM_001886.3	c.40-11del		intron_variant		ENST00000354760.4	NP_001877.1
CRYBA4	XM_006724140.4	c.55-11del		intron_variant			XP_006724203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBA4	ENST00000354760.4	c.40-11del		intron_variant		1	NM_001886.3	ENSP00000346805	P1
CRYBA4	ENST00000466315.1	n.55+588del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 150460 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000293

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000296

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00282 AC: 3276 AN: 1160634 Hom.: 0 Cov.: 29 AF XY: 0.00272 AC XY: 1579 AN XY: 580190

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.000959

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.000881

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00605

Gnomad4 NFE exome AF: 0.00304

Gnomad4 OTH exome AF: 0.00258

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000930 AC: 14 AN: 150562 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73474

Gnomad4 AFR AF: 0.0000729

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000293

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00145

Alfa AF: 0.0166 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cataract 23 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs746964125; hg19: chr22-27019177;