GeneBe

rs771277920

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024596.5(MCPH1):​c.-5C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MCPH1
NM_024596.5 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

0 publications found
Variant links:
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]
MCPH1-DT (HGNC:55599): (MCPH1 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MCPH1NM_024596.5 linkc.-5C>A 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 14 ENST00000344683.10 NP_078872.3 Q8NEM0-1
MCPH1NM_024596.5 linkc.-5C>A 5_prime_UTR_variant Exon 1 of 14 ENST00000344683.10 NP_078872.3 Q8NEM0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MCPH1ENST00000344683.10 linkc.-5C>A 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 14 1 NM_024596.5 ENSP00000342924.5 Q8NEM0-1
MCPH1ENST00000344683.10 linkc.-5C>A 5_prime_UTR_variant Exon 1 of 14 1 NM_024596.5 ENSP00000342924.5 Q8NEM0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459938
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726260
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33448
American (AMR)
AF:
0.00
AC:
0
AN:
44646
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26042
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39658
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86080
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52512
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5740
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111504
Other (OTH)
AF:
0.00
AC:
0
AN:
60308
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
9.0
DANN
Benign
0.84
PhyloP100
-1.2
PromoterAI
-0.15
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs771277920; hg19: chr8-6264184; API