2-208145688-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAA

Variant names:

• chr2-208145688-C-CAAAAA
• rs554918356
• NM_005210.4:c.252+81_252+85dupTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005210.4(CRYGB):​c.252+81_252+85dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,284,602 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000019 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: CRYGB NM_005210.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489

Genes affected

CRYGB (HGNC:2409): (crystallin gamma B) 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. Gamma-crystallins are a homogeneous group of highly symmetrical, monomeric proteins typically lacking connecting peptides and terminal extensions. They are differentially regulated after early development. Four gamma-crystallin genes (gamma-A through gamma-D) and three pseudogenes (gamma-E, gamma-F, gamma-G) are tandemly organized in a genomic segment as a gene cluster. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]

LOC100507443 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYGB	NM_005210.4	c.252+81_252+85dupTTTTT		intron_variant	Intron 2 of 2	ENST00000260988.5	NP_005201.2
CRYGB	XM_017003402.2	c.258+75_258+79dupTTTTT		intron_variant	Intron 2 of 2		XP_016858891.1
LOC100507443	NR_038437.1	n.221+8528_221+8532dupAAAAA		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYGB	ENST00000260988.5	c.252+85_252+86insTTTTT		intron_variant	Intron 2 of 2	1	NM_005210.4	ENSP00000260988.4

Frequencies

GnomAD3 genomes AF: 0.0000187 AC: 1 AN: 53456 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000372

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000569 AC: 7 AN: 1231154 Hom.: 0 AF XY: 0.00000666 AC XY: 4 AN XY: 600822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000389

Gnomad4 ASJ exome AF: 0.0000560

Gnomad4 EAS exome AF: 0.0000299

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000407

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000187 AC: 1 AN: 53448 Hom.: 0 Cov.: 22 AF XY: 0.0000401 AC XY: 1 AN XY: 24908

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000372

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs554918356; hg19: chr2-209010412;