rs2433150

chr8-6644631-G-Achr8-6644631-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024596.5(MCPH1):c.*1582G>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 0.197 in 152,056 control chromosomes in the GnomAD database, including 3,087 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 (3087 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: MCPH1 NM_024596.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1	NM_024596.5	c.*1582G>A		3_prime_UTR_variant	14/14	ENST00000344683.10
MCPH1-AS1	NR_125386.1	n.70-17321C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCPH1	ENST00000344683.10	c.*1582G>A		3_prime_UTR_variant	14/14	1	NM_024596.5	P1
MCPH1-AS1	ENST00000661193.1	n.70-9212C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29895 AN: 151930 Hom.: 3081 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.197 AC: 29928 AN: 152046 Hom.: 3087 Cov.: 32 AF XY: 0.196 AC XY: 14588 AN XY: 74312

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0887

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.185

Alfa AF: 0.193 Hom.: 3961

Bravo AF: 0.192

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.8
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs2433150; hg19: chr8-6502152;