rs17570753

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024596.5(MCPH1):​c.*1789T>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 0.0646 in 152,076 control chromosomes in the GnomAD database, including 397 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 0.065 ( 397 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MCPH1
NM_024596.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0190
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]

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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=-0.79).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MCPH1NM_024596.5 linkuse as main transcriptc.*1789T>A 3_prime_UTR_variant 14/14 ENST00000344683.10 NP_078872.3 Q8NEM0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MCPH1ENST00000344683.10 linkuse as main transcriptc.*1789T>A 3_prime_UTR_variant 14/141 NM_024596.5 ENSP00000342924.5 Q8NEM0-1

Frequencies

GnomAD3 genomes
AF:
0.0647
AC:
9827
AN:
151958
Hom.:
398
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0328
Gnomad AMI
AF:
0.0658
Gnomad AMR
AF:
0.0564
Gnomad ASJ
AF:
0.123
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.0964
Gnomad FIN
AF:
0.0429
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.0881
Gnomad OTH
AF:
0.0798
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
4
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2
Gnomad4 AFR exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0646
AC:
9831
AN:
152076
Hom.:
397
Cov.:
32
AF XY:
0.0629
AC XY:
4675
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0327
Gnomad4 AMR
AF:
0.0564
Gnomad4 ASJ
AF:
0.123
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.0975
Gnomad4 FIN
AF:
0.0429
Gnomad4 NFE
AF:
0.0881
Gnomad4 OTH
AF:
0.0789
Alfa
AF:
0.0762
Hom.:
66
Bravo
AF:
0.0642
Asia WGS
AF:
0.0470
AC:
163
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.96
DANN
Benign
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17570753; hg19: chr8-6502359; COSMIC: COSV60916125; COSMIC: COSV60916125; API