rs12677501

Positions:

• chr8-6481143-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000344683.10(MCPH1):​c.2136+267T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,152 control chromosomes in the GnomAD database, including 1,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (1994 hom., cov: 32)
• Consequence: MCPH1 ENST00000344683.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-6481143-T-G is Benign according to our data. Variant chr8-6481143-T-G is described in ClinVar as [Benign]. Clinvar id is 1265419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCPH1	NM_024596.5	c.2136+267T>G		intron_variant		ENST00000344683.10	NP_078872.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCPH1	ENST00000344683.10	c.2136+267T>G		intron_variant		1	NM_024596.5	ENSP00000342924	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23783 AN: 152034 Hom.: 1994 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.156 AC: 23789 AN: 152152 Hom.: 1994 Cov.: 32 AF XY: 0.153 AC XY: 11417 AN XY: 74388

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0963

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.178

Alfa AF: 0.162 Hom.: 336

Bravo AF: 0.156

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.12
DANN	Benign	0.60

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: rs12677501; hg19: chr8-6338664;