1-207752250-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_172351.3(CD46):c.38C>T(p.Ser13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,152 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 55 hom. )
Consequence
CD46
NM_172351.3 missense
NM_172351.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: -0.449
Genes affected
CD46 (HGNC:6953): (CD46 molecule) The protein encoded by this gene is a type I membrane protein and is a regulatory part of the complement system. The encoded protein has cofactor activity for inactivation of complement components C3b and C4b by serum factor I, which protects the host cell from damage by complement. In addition, the encoded protein can act as a receptor for the Edmonston strain of measles virus, human herpesvirus-6, and type IV pili of pathogenic Neisseria. Finally, the protein encoded by this gene may be involved in the fusion of the spermatozoa with the oocyte during fertilization. Mutations at this locus have been associated with susceptibility to hemolytic uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2010]
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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 (MetaRNN=0.003166467).
BP6
?
Variant 1-207752250-C-T is Benign according to our data. Variant chr1-207752250-C-T is described in ClinVar as [Benign]. Clinvar id is 875708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207752250-C-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00305 (465/152372) while in subpopulation EAS AF= 0.0359 (186/5180). AF 95% confidence interval is 0.0317. There are 4 homozygotes in gnomad4. There are 248 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 4 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD46 | NM_172351.3 | c.38C>T | p.Ser13Phe | missense_variant | 1/13 | ENST00000367042.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD46 | ENST00000367042.6 | c.38C>T | p.Ser13Phe | missense_variant | 1/13 | 1 | NM_172351.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00303 AC: 462AN: 152254Hom.: 4 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00510 AC: 1282AN: 251418Hom.: 21 AF XY: 0.00418 AC XY: 568AN XY: 135900
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GnomAD4 exome AF: 0.00197 AC: 2883AN: 1461780Hom.: 55 Cov.: 31 AF XY: 0.00188 AC XY: 1366AN XY: 727210
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 02, 2022 | - - |
CD46-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2019 | 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). - |
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Atypical hemolytic-uremic syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 25, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;T;D;T;T;D;T;T;D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;L;L;L;L
MutationTaster
Benign
N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T;D;T;T
Sift4G
Benign
T;T;T;T;T;T;T;D;T;T
Polyphen
D;B;B;B;D;B;B;.;B;D
Vest4
MVP
MPC
0.23
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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