8-47960493-CG-C
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The ENST00000518221.5(MCM4):c.-15+174delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 152,172 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)
Consequence
MCM4
ENST00000518221.5 intron
ENST00000518221.5 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.466
Genes affected
MCM4 (HGNC:6947): (minichromosome maintenance complex component 4) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00393 (598/152172) while in subpopulation SAS AF= 0.0241 (116/4814). AF 95% confidence interval is 0.0205. There are 4 homozygotes in gnomad4. There are 304 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 4 AR gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|
Ensembl
Frequencies
GnomAD3 genomes 0.00391 AC: 594AN: 152054Hom.: 4 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.00393 AC: 598AN: 152172Hom.: 4 Cov.: 32 AF XY: 0.00409 AC XY: 304AN XY: 74396
GnomAD4 genome
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32
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74396
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at