rs1054073
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The ENST00000519480.6(MCPH1):c.*435T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 977,376 control chromosomes in the GnomAD database, including 309,827 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 0.69 ( 39457 hom., cov: 33)
Exomes 𝑓: 0.81 ( 270370 hom. )
Consequence
MCPH1
ENST00000519480.6 3_prime_UTR
ENST00000519480.6 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.256
Genes affected
MCPH1 (HGNC:6954): (microcephalin 1) This gene encodes a DNA damage response protein. The encoded protein may play a role in G2/M checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. Mutations in this gene have been associated with primary autosomal recessive microcephaly 1 and premature chromosome condensation syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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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=-0.93).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.1825+443T>A | intron_variant | ENST00000344683.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.1825+443T>A | intron_variant | 1 | NM_024596.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.694 AC: 105472AN: 152030Hom.: 39447 Cov.: 33
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GnomAD4 exome AF: 0.807 AC: 665687AN: 825228Hom.: 270370 Cov.: 18 AF XY: 0.807 AC XY: 307703AN XY: 381270
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GnomAD4 genome ? AF: 0.693 AC: 105507AN: 152148Hom.: 39457 Cov.: 33 AF XY: 0.702 AC XY: 52195AN XY: 74382
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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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