Variant rs1550697 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 NM_024596.5(MCPH1):c.23-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,569,786 control chromosomes in the GnomAD database, including 51,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 10445 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40994 hom. )

Consequence

MCPH1
NM_024596.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.36

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:

Genome browser will be placed here

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 8-6409253-G-A is Benign according to our data. Variant chr8-6409253-G-A is described in ClinVar as [Benign]. Clinvar id is 158854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-6409253-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCPH1	NM_024596.5 linkuse as main transcript	c.23-26G>A		intron_variant		ENST00000344683.10	NP_078872.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCPH1	ENST00000344683.10 linkuse as main transcript	c.23-26G>A		intron_variant		1	NM_024596.5	ENSP00000342924	P1	Q8NEM0-1

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49785

AN:

151902

Hom.:

10413

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.315

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.251

AC:

62496

AN:

249246

Hom.:

9272

AF XY:

0.246

AC XY:

33213

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.614

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.304

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.120

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.230

AC:

325397

AN:

1417766

Hom.:

40994

Cov.:

AF XY:

0.230

AC XY:

162640

AN XY:

708232

show subpopulations

Gnomad4 AFR exome

AF:

0.619

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.324

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.328

AC:

49861

AN:

152020

Hom.:

10445

Cov.:

AF XY:

0.321

AC XY:

23876

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.602

Gnomad4 AMR

AF:

0.268

Gnomad4 ASJ

AF:

0.315

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.123

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.241

Hom.:

6300

Bravo

AF:

0.349

Asia WGS

AF:

0.297

AC:

1036

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Jul 03, 2018	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

- -

Microcephaly 1, primary, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.81

DANN

Benign

0.84

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