8-47960701-A-C

Position:

• chr8-47960701-A-C

Variant summary

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

The ENST00000518221.5(MCM4):​c.-15+381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,186 control chromosomes in the GnomAD database, including 7,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (7487 hom., cov: 32)
• Consequence: MCM4 ENST00000518221.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.57

Genes affected

MCM4 (HGNC:6947): (minichromosome maintenance complex component 4) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-47960701-A-C is Benign according to our data. Variant chr8-47960701-A-C is described in ClinVar as [Benign]. Clinvar id is 363199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM4	ENST00000518221.5	c.-15+381A>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34162 AN: 152068 Hom.: 7476 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.225 AC: 34234 AN: 152186 Hom.: 7487 Cov.: 32 AF XY: 0.223 AC XY: 16599 AN XY: 74434

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.0454

Gnomad4 NFE AF: 0.0560

Gnomad4 OTH AF: 0.218

Alfa AF: 0.0844 Hom.: 1454

Bravo AF: 0.258

Asia WGS AF: 0.225 AC: 781 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.072
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1551655; hg19: chr8-48873261;