rs309180
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000264156.3(MCM6):c.1626+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,597,080 control chromosomes in the GnomAD database, including 380,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.50 ( 23211 hom., cov: 30)
Exomes 𝑓: 0.68 ( 357574 hom. )
Consequence
MCM6
ENST00000264156.3 intron
ENST00000264156.3 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.118
Genes affected
MCM6 (HGNC:6949): (minichromosome maintenance complex component 6) 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 the 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, 4 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Single nucleotide polymorphisms in the intron regions of this gene are associated with differential transcriptional activation of the promoter of the neighboring lactase gene and, thereby, influence lactose intolerance in early adulthood. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MCM6 | NM_005915.6 | c.1626+43C>T | intron_variant | ENST00000264156.3 | NP_005906.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MCM6 | ENST00000264156.3 | c.1626+43C>T | intron_variant | 1 | NM_005915.6 | ENSP00000264156 | P1 | |||
MCM6 | ENST00000492091.1 | n.182-5122C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.502 AC: 76170AN: 151798Hom.: 23210 Cov.: 30
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GnomAD3 exomes AF: 0.538 AC: 129126AN: 240140Hom.: 40034 AF XY: 0.539 AC XY: 69944AN XY: 129654
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GnomAD4 exome AF: 0.679 AC: 981829AN: 1445164Hom.: 357574 Cov.: 26 AF XY: 0.667 AC XY: 479604AN XY: 718606
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GnomAD4 genome AF: 0.501 AC: 76184AN: 151916Hom.: 23211 Cov.: 30 AF XY: 0.493 AC XY: 36583AN XY: 74224
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at