8-6630984-T-C

Variant names:

• chr8-6630984-T-C
• rs2911968
• NM_024596.5:c.2452+9293T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024596.5(MCPH1):​c.2452+9293T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,968 control chromosomes in the GnomAD database, including 17,672 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 0.47 (17672 hom., cov: 32)
• Consequence: MCPH1 NM_024596.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 6 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCPH1	NM_024596.5	c.2452+9293T>C		intron_variant	Intron 13 of 13	ENST00000344683.10	NP_078872.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCPH1	ENST00000344683.10	c.2452+9293T>C		intron_variant	Intron 13 of 13	1	NM_024596.5	ENSP00000342924.5

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71374 AN: 151850 Hom.: 17631 Cov.: 32

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71469 AN: 151968 Hom.: 17672 Cov.: 32 AF XY: 0.474 AC XY: 35218 AN XY: 74256

African (AFR) AF: 0.619 AC: 25653 AN: 41466

American (AMR) AF: 0.444 AC: 6778 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3725 AN: 5166

South Asian (SAS) AF: 0.490 AC: 2364 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4224 AN: 10534

Middle Eastern (MID) AF: 0.359 AC: 104 AN: 290

European-Non Finnish (NFE) AF: 0.385 AC: 26180 AN: 67952

Other (OTH) AF: 0.450 AC: 946 AN: 2104

Alfa AF: 0.416 Hom.: 7974

Bravo AF: 0.477

Asia WGS AF: 0.566 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.6
DANN	Benign	0.73
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2911968; hg19: chr8-6488505;