18-50261232-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_145020.5(CFAP53):c.305G>A(p.Arg102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,461,570 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0066 ( 8 hom., cov: 28)
Exomes 𝑓: 0.00067 ( 11 hom. )
Consequence
CFAP53
NM_145020.5 missense
NM_145020.5 missense
Scores
3
4
10
Clinical Significance
Conservation
PhyloP100: 2.46
Genes affected
CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]
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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=0.007839054).
BP6
Variant 18-50261232-C-T is Benign according to our data. Variant chr18-50261232-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50261232-C-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00662 (916/138446) while in subpopulation AFR AF= 0.0233 (849/36492). AF 95% confidence interval is 0.022. There are 8 homozygotes in gnomad4. There are 407 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFAP53 | NM_145020.5 | c.305G>A | p.Arg102His | missense_variant | 3/8 | ENST00000398545.5 | NP_659457.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFAP53 | ENST00000398545.5 | c.305G>A | p.Arg102His | missense_variant | 3/8 | 1 | NM_145020.5 | ENSP00000381553 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00656 AC: 908AN: 138392Hom.: 8 Cov.: 28
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GnomAD3 exomes AF: 0.00197 AC: 281AN: 142736Hom.: 4 AF XY: 0.00147 AC XY: 119AN XY: 80892
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GnomAD4 exome AF: 0.000667 AC: 883AN: 1323124Hom.: 11 Cov.: 36 AF XY: 0.000614 AC XY: 401AN XY: 652692
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GnomAD4 genome AF: 0.00662 AC: 916AN: 138446Hom.: 8 Cov.: 28 AF XY: 0.00614 AC XY: 407AN XY: 66258
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Heterotaxy, visceral, 6, autosomal Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 26, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
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T
GERP RS
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