chr11-45847462-C-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The ENST00000443527.6(CRY2):c.35C>A(p.Ala12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,596,242 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0071 ( 47 hom., cov: 33)
Exomes 𝑓: 0.0028 ( 96 hom. )
Consequence
CRY2
ENST00000443527.6 missense
ENST00000443527.6 missense
Scores
2
1
11
Clinical Significance
Conservation
PhyloP100: 1.62
Genes affected
CRY2 (HGNC:2385): (cryptochrome circadian regulator 2) This gene encodes a flavin adenine dinucleotide-binding protein that is a key component of the circadian core oscillator complex, which regulates the circadian clock. This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. Polymorphisms in this gene have been associated with altered sleep patterns. The encoded protein is widely conserved across plants and animals. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]
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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 (MetaRNN=0.0022559166).
BP6
?
Variant 11-45847462-C-A is Benign according to our data. Variant chr11-45847462-C-A is described in ClinVar as [Benign]. Clinvar id is 782294.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRY2 | NM_001127457.3 | c.32+181C>A | intron_variant | ||||
CRY2 | NM_021117.5 | upstream_gene_variant | ENST00000616080.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRY2 | ENST00000616080.2 | upstream_gene_variant | 1 | NM_021117.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00710 AC: 1081AN: 152206Hom.: 47 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0106 AC: 2387AN: 225630Hom.: 76 AF XY: 0.00850 AC XY: 1058AN XY: 124540
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GnomAD4 exome AF: 0.00277 AC: 4000AN: 1443916Hom.: 96 Cov.: 36 AF XY: 0.00255 AC XY: 1826AN XY: 717016
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GnomAD4 genome ? AF: 0.00714 AC: 1088AN: 152326Hom.: 47 Cov.: 33 AF XY: 0.00904 AC XY: 673AN XY: 74488
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Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;D
Vest4
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at