rs3020264

Positions:

• chr8-6631056-G-A
• chr8-6631056-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.2452+9365G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,076 control chromosomes in the GnomAD database, including 4,481 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 0.24 (4481 hom., cov: 32)
• Consequence: MCPH1 NM_024596.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCPH1	NM_024596.5	c.2452+9365G>A		intron_variant		ENST00000344683.10
MCPH1-AS1	NR_125386.1	n.70-3746C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCPH1	ENST00000344683.10	c.2452+9365G>A		intron_variant		1	NM_024596.5	P1
MCPH1-AS1	ENST00000661193.1	n.894+3539C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36194 AN: 151958 Hom.: 4479 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.238 AC: 36219 AN: 152076 Hom.: 4481 Cov.: 32 AF XY: 0.237 AC XY: 17601 AN XY: 74312

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.0892

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.240

Alfa AF: 0.262 Hom.: 9324

Bravo AF: 0.227

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.57

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: rs3020264; hg19: chr8-6488577;