dbSNP rs2253560: MCPH1:c.2215-494G>A (chr8-6620960-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024596.5(MCPH1):c.2215-494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 191,354 control chromosomes in the GnomAD database, including 4,128 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 0.20 ( 3571 hom., cov: 32)

Exomes 𝑓: 0.16 ( 557 hom. )

Consequence

MCPH1
NM_024596.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.714

Publications

5 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 links:

MCPH1-AS1 (HGNC:51655): (MCPH1 antisense RNA 1)

MCPH1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCPH1	NM_024596.5 link	c.2215-494G>A		intron_variant	Intron 12 of 13	ENST00000344683.10	NP_078872.3	Q8NEM0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCPH1	ENST00000344683.10 link	c.2215-494G>A		intron_variant	Intron 12 of 13	1	NM_024596.5	ENSP00000342924.5		Q8NEM0-1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29978

AN:

152002

Hom.:

3574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0741

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.159

AC:

6244

AN:

39232

Hom.:

557

Cov.:

AF XY:

0.160

AC XY:

3309

AN XY:

20740

show subpopulations

African (AFR)

AF:

0.0379

AC:

AN:

660

American (AMR)

AF:

0.134

AC:

440

AN:

3278

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

AN:

786

East Asian (EAS)

AF:

0.0492

AC:

AN:

1950

South Asian (SAS)

AF:

0.154

AC:

825

AN:

5354

European-Finnish (FIN)

AF:

0.141

AC:

190

AN:

1344

Middle Eastern (MID)

AF:

0.147

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.179

AC:

4254

AN:

23826

Other (OTH)

AF:

0.159

AC:

308

AN:

1932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

207

414

620

827

1034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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

AF:

0.197

AC:

29978

AN:

152122

Hom.:

3571

Cov.:

AF XY:

0.196

AC XY:

14572

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0718

AC:

2982

AN:

41512

American (AMR)

AF:

0.163

AC:

2494

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

774

AN:

3468

East Asian (EAS)

AF:

0.0741

AC:

384

AN:

5182

South Asian (SAS)

AF:

0.240

AC:

1153

AN:

4806

European-Finnish (FIN)

AF:

0.251

AC:

2650

AN:

10574

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18813

AN:

67986

Other (OTH)

AF:

0.212

AC:

447

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1209

2417

3626

4834

6043

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

4140

Bravo

AF:

0.184

Asia WGS

AF:

0.159

AC:

554

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.32

(source)

DANN

Benign

0.58

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over