chr3-186539251-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_017541.4(CRYGS):c.264+104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,502,386 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0056 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00055 ( 9 hom. )
Consequence
CRYGS
NM_017541.4 intron
NM_017541.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.610
Genes affected
CRYGS (HGNC:2417): (crystallin gamma S) 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. This gene encodes a protein initially considered to be a beta-crystallin but the encoded protein is monomeric and has greater sequence similarity to other gamma-crystallins. This gene encodes the most significant gamma-crystallin in adult eye lens tissue. Whether due to aging or mutations in specific genes, gamma-crystallins have been involved in cataract formation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 3-186539251-C-T is Benign according to our data. Variant chr3-186539251-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1199084.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00559 (852/152306) while in subpopulation AFR AF= 0.0198 (822/41560). AF 95% confidence interval is 0.0187. There are 11 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 852 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYGS | NM_017541.4 | c.264+104G>A | intron_variant | ENST00000307944.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYGS | ENST00000307944.6 | c.264+104G>A | intron_variant | 1 | NM_017541.4 | P1 | |||
CRYGS | ENST00000460288.1 | n.1166+104G>A | intron_variant, non_coding_transcript_variant | 1 | |||||
CRYGS | ENST00000392499.6 | c.264+104G>A | intron_variant | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00560 AC: 852AN: 152188Hom.: 11 Cov.: 32
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GnomAD4 exome AF: 0.000554 AC: 748AN: 1350080Hom.: 9 AF XY: 0.000518 AC XY: 351AN XY: 677248
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 26, 2020 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at