GeneBe

8-6406744-C-T

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.22+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,445,882 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: 0.0000021 ( 0 hom. )

Consequence

MCPH1
NM_024596.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.94

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=-0.82).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MCPH1NM_024596.5 linkc.22+55C>T intron_variant Intron 1 of 13 ENST00000344683.10 NP_078872.3 Q8NEM0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MCPH1ENST00000344683.10 linkc.22+55C>T intron_variant Intron 1 of 13 1 NM_024596.5 ENSP00000342924.5 Q8NEM0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000207
AC:
3
AN:
1445882
Hom.:
0
Cov.:
29
AF XY:
0.00000417
AC XY:
3
AN XY:
719256
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33258
American (AMR)
AF:
0.00
AC:
0
AN:
43998
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25804
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39432
South Asian (SAS)
AF:
0.0000236
AC:
2
AN:
84744
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51832
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5646
European-Non Finnish (NFE)
AF:
9.08e-7
AC:
1
AN:
1101336
Other (OTH)
AF:
0.00
AC:
0
AN:
59832
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
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
-0.82
CADD
Benign
0.78
DANN
Benign
0.70
PhyloP100
-3.9
PromoterAI
-0.0052
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs140026083; hg19: chr8-6264265; COSMIC: COSV60909468; COSMIC: COSV60909468; API