rs529607771
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000096.4(CP):c.2611G>A(p.Asp871Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000407 in 1,613,696 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00043 ( 13 hom. )
Consequence
CP
NM_000096.4 missense
NM_000096.4 missense
Scores
2
11
5
Clinical Significance
Conservation
PhyloP100: 4.33
Genes affected
CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009948522).
BP6
?
Variant 3-149179606-C-T is Benign according to our data. Variant chr3-149179606-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 343753.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Likely_benign=1, Uncertain_significance=1}.
BS2
?
High Homozygotes in GnomAdExome4 at 13 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CP | NM_000096.4 | c.2611G>A | p.Asp871Asn | missense_variant | 15/19 | ENST00000264613.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CP | ENST00000264613.11 | c.2611G>A | p.Asp871Asn | missense_variant | 15/19 | 1 | NM_000096.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 151988Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000963 AC: 242AN: 251260Hom.: 2 AF XY: 0.00122 AC XY: 166AN XY: 135804
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GnomAD4 exome AF: 0.000432 AC: 632AN: 1461592Hom.: 13 Cov.: 31 AF XY: 0.000597 AC XY: 434AN XY: 727110
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74338
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Deficiency of ferroxidase Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 22, 2017 | - - |
CP-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Pathogenic
D
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Vest4
0.54
MutPred
0.49
.;Loss of catalytic residue at D871 (P = 0.0201);.;
MVP
MPC
0.43
ClinPred
T
GERP RS
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