rs2071860

Variant names:

• chr22-26623164-C-T
• rs2071860
• NM_001886.3:c.40-70C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-26623164-C-T
• chr22-26623164-C-A

Variant summary

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

The NM_001886.3(CRYBA4):​c.40-70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,294,130 control chromosomes in the GnomAD database, including 92,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9051 hom., cov: 32)
  • Exomes 𝑓: 0.38 (83176 hom.)
• Consequence: CRYBA4 NM_001886.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.166
• Publications: 15 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: G2P, Labcorp Genetics (formerly Invitae), 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-26623164-C-T is Benign according to our data. Variant chr22-26623164-C-T is described in ClinVar as Benign. ClinVar VariationId is 677163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001886.3. 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
	CRYBA4	NM_001886.3	MANE Select	c.40-70C>T		intron	N/A	NP_001877.1	A0A097PIJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBA4	ENST00000354760.4	TSL:1 MANE Select	c.40-70C>T		intron	N/A	ENSP00000346805.3	P53673
	CRYBA4	ENST00000466315.1	TSL:5	n.55+529C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50646 AN: 151940 Hom.: 9042 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.377 AC: 430201 AN: 1142072 Hom.: 83176 AF XY: 0.378 AC XY: 220529 AN XY: 583044

African (AFR) AF: 0.198 AC: 5469 AN: 27588

American (AMR) AF: 0.565 AC: 25042 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 10137 AN: 24200

East Asian (EAS) AF: 0.377 AC: 14441 AN: 38286

South Asian (SAS) AF: 0.442 AC: 35264 AN: 79852

European-Finnish (FIN) AF: 0.344 AC: 14906 AN: 43282

Middle Eastern (MID) AF: 0.419 AC: 2047 AN: 4890

European-Non Finnish (NFE) AF: 0.367 AC: 304421 AN: 829640

Other (OTH) AF: 0.369 AC: 18474 AN: 50030

GnomAD4 genome AF: 0.333 AC: 50696 AN: 152058 Hom.: 9051 Cov.: 32 AF XY: 0.336 AC XY: 24961 AN XY: 74324

African (AFR) AF: 0.209 AC: 8682 AN: 41472

American (AMR) AF: 0.441 AC: 6751 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1905 AN: 5170

South Asian (SAS) AF: 0.435 AC: 2098 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3772 AN: 10554

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24821 AN: 67960

Other (OTH) AF: 0.389 AC: 821 AN: 2112

Alfa AF: 0.365 Hom.: 32404

Bravo AF: 0.338

Asia WGS AF: 0.411 AC: 1431 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	-0.92
CADD	Benign	1.3
DANN	Benign	0.78
PhyloP100		-0.17
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: rs2071860; hg19: chr22-27019128; COSMIC: COSV61322384;