Variant 8-6406609-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000519480.6(MCPH1):c.-59G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,590,766 control chromosomes in the GnomAD database, including 448,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 33640 hom., cov: 34)

Exomes 𝑓: 0.75 ( 414660 hom. )

Consequence

MCPH1
ENST00000519480.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.357

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 links:

MCPH1-DT (HGNC:55599): (MCPH1 divergent transcript)

MCPH1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-6406609-G-C is Benign according to our data. Variant chr8-6406609-G-C is described in ClinVar as [Benign]. Clinvar id is 363515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1	NM_024596.5 linkuse as main transcript			upstream_gene_variant		ENST00000344683.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCPH1	ENST00000344683.10 linkuse as main transcript			upstream_gene_variant		1	NM_024596.5	P1	Q8NEM0-1
MCPH1-DT	ENST00000500118.4 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

97008

AN:

151938

Hom.:

33638

Cov.:

show subpopulations

Gnomad AFR

AF:

0.375

Gnomad AMI

AF:

0.939

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.792

Gnomad MID

AF:

0.662

Gnomad NFE

AF:

0.792

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.753

AC:

1083070

AN:

1438710

Hom.:

414660

Cov.:

AF XY:

0.751

AC XY:

536670

AN XY:

714296

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.543

Gnomad4 ASJ exome

AF:

0.690

Gnomad4 EAS exome

AF:

0.489

Gnomad4 SAS exome

AF:

0.625

Gnomad4 FIN exome

AF:

0.810

Gnomad4 NFE exome

AF:

0.792

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.638

AC:

97040

AN:

152056

Hom.:

33640

Cov.:

AF XY:

0.635

AC XY:

47213

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.589

Gnomad4 ASJ

AF:

0.688

Gnomad4 EAS

AF:

0.478

Gnomad4 SAS

AF:

0.622

Gnomad4 FIN

AF:

0.792

Gnomad4 NFE

AF:

0.792

Gnomad4 OTH

AF:

0.645

Alfa

AF:

0.705

Hom.:

4944

Bravo

AF:

0.613

Asia WGS

AF:

0.568

AC:

1974

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	- -

Primary Microcephaly, Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.3

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over