rs5744539
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001130105.1(CERT1):c.301G>A(p.Asp101Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,566,594 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 48 hom. )
Consequence
CERT1
NM_001130105.1 missense
NM_001130105.1 missense
Scores
2
9
Clinical Significance
Conservation
PhyloP100: 1.04
Genes affected
CERT1 (HGNC:2205): (ceramide transporter 1) This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
POLK (HGNC:9183): (DNA polymerase kappa) This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]
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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=0.0024900734).
BP6
Variant 5-75511291-C-T is Benign according to our data. Variant chr5-75511291-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 446020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-75511291-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0028 (426/152252) while in subpopulation AMR AF= 0.0217 (332/15300). AF 95% confidence interval is 0.0198. There are 9 homozygotes in gnomad4. There are 211 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 426 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CERT1 | NM_001379029.1 | c.-84G>A | 5_prime_UTR_variant | 1/17 | ENST00000643780.2 | NP_001365958.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CERT1 | ENST00000643780.2 | c.-84G>A | 5_prime_UTR_variant | 1/17 | NM_001379029.1 | ENSP00000495760.1 |
Frequencies
GnomAD3 genomes AF: 0.00277 AC: 422AN: 152134Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00960 AC: 1603AN: 166936Hom.: 34 AF XY: 0.00713 AC XY: 647AN XY: 90708
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GnomAD4 exome AF: 0.00150 AC: 2123AN: 1414342Hom.: 48 Cov.: 32 AF XY: 0.00126 AC XY: 880AN XY: 699556
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GnomAD4 genome AF: 0.00280 AC: 426AN: 152252Hom.: 9 Cov.: 32 AF XY: 0.00283 AC XY: 211AN XY: 74444
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 24, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
Polyphen
B
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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