rs226052
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001376256.1(CRYM):c.490-12C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,613,984 control chromosomes in the GnomAD database, including 3,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.087 ( 1918 hom., cov: 32)
Exomes 𝑓: 0.0096 ( 1703 hom. )
Consequence
CRYM
NM_001376256.1 splice_polypyrimidine_tract, intron
NM_001376256.1 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00003459
2
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
CRYM (HGNC:2418): (crystallin mu) Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Mutations in this gene have been associated with autosomal dominant non-syndromic deafness. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 16-21267749-G-A is Benign according to our data. Variant chr16-21267749-G-A is described in ClinVar as [Benign]. Clinvar id is 44240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-21267749-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRYM | NM_001376256.1 | c.490-12C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000572914.2 | |||
CRYM | NM_001888.5 | c.490-12C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRYM | ENST00000572914.2 | c.490-12C>T | splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_001376256.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0867 AC: 13191AN: 152120Hom.: 1909 Cov.: 32
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GnomAD3 exomes AF: 0.0231 AC: 5808AN: 251278Hom.: 777 AF XY: 0.0173 AC XY: 2348AN XY: 135806
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GnomAD4 exome AF: 0.00959 AC: 14020AN: 1461746Hom.: 1703 Cov.: 31 AF XY: 0.00831 AC XY: 6044AN XY: 727178
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GnomAD4 genome ? AF: 0.0870 AC: 13238AN: 152238Hom.: 1918 Cov.: 32 AF XY: 0.0840 AC XY: 6250AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | 490-12C>T in Intron 06 of CRYM: This variant is not expected to have clinical si gnificance because it has been identified in 27.9% (1043/3738) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs226052). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at