chr1-193122189-AG-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_024529.5(CDC73):c.-4del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000214 in 1,608,924 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00084 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )
Consequence
CDC73
NM_024529.5 5_prime_UTR
NM_024529.5 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.51
Genes affected
CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 1-193122189-AG-A is Benign according to our data. Variant chr1-193122189-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 506631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-193122189-AG-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000837 (127/151816) while in subpopulation AFR AF= 0.00285 (118/41388). AF 95% confidence interval is 0.00243. There are 1 homozygotes in gnomad4. There are 51 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 128 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDC73 | NM_024529.5 | c.-4del | 5_prime_UTR_variant | 1/17 | ENST00000367435.5 | ||
CDC73 | XM_006711537.5 | c.-4del | 5_prime_UTR_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDC73 | ENST00000367435.5 | c.-4del | 5_prime_UTR_variant | 1/17 | 1 | NM_024529.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000844 AC: 128AN: 151700Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000261 AC: 64AN: 244892Hom.: 0 AF XY: 0.000180 AC XY: 24AN XY: 133210
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GnomAD4 exome AF: 0.000150 AC: 218AN: 1457108Hom.: 1 Cov.: 32 AF XY: 0.000150 AC XY: 109AN XY: 724608
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GnomAD4 genome ? AF: 0.000837 AC: 127AN: 151816Hom.: 1 Cov.: 32 AF XY: 0.000687 AC XY: 51AN XY: 74226
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at