Variant rs2307355 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005916.5(MCM7):c.1440C>T(p.Ala480Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,613,974 control chromosomes in the GnomAD database, including 1,611 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 0.040 ( 125 hom., cov: 32)

Exomes 𝑓: 0.044 ( 1486 hom. )

Consequence

MCM7
NM_005916.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.525

Variant links:

Genes affected

MCM7 (HGNC:6950): (minichromosome maintenance complex component 7) 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 the 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, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MCM7 links:

MCM7 (HGNC:):

MCM7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=0.525 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM7	NM_005916.5 linkuse as main transcript	c.1440C>T	p.Ala480Ala	synonymous_variant	11/15	ENST00000303887.10	NP_005907.3	P33993-1C6EMX8A0A0S2Z4A5
MCM7	NM_001278595.2 linkuse as main transcript	c.912C>T	p.Ala304Ala	synonymous_variant	10/14		NP_001265524.1	P33993-3C6EMX8
MCM7	NM_182776.3 linkuse as main transcript	c.912C>T	p.Ala304Ala	synonymous_variant	10/14		NP_877577.1	P33993-3
MCM7	XM_005250348.4 linkuse as main transcript	c.1119C>T	p.Ala373Ala	synonymous_variant	11/15		XP_005250405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM7	ENST00000303887.10 linkuse as main transcript	c.1440C>T	p.Ala480Ala	synonymous_variant	11/15	1	NM_005916.5	ENSP00000307288.5		P33993-1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6060

AN:

152148

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0469

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.0376

Gnomad SAS

AF:

0.0564

Gnomad FIN

AF:

0.0307

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0454

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0419

AC:

10521

AN:

251218

Hom.:

252

AF XY:

0.0424

AC XY:

5755

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0292

Gnomad AMR exome

AF:

0.0298

Gnomad ASJ exome

AF:

0.0318

Gnomad EAS exome

AF:

0.0406

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0340

Gnomad NFE exome

AF:

0.0468

Gnomad OTH exome

AF:

0.0497

GnomAD4 exome

AF:

0.0438

AC:

63991

AN:

1461708

Hom.:

1486

Cov.:

AF XY:

0.0440

AC XY:

31983

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0289

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.0328

Gnomad4 EAS exome

AF:

0.0421

Gnomad4 SAS exome

AF:

0.0508

Gnomad4 FIN exome

AF:

0.0374

Gnomad4 NFE exome

AF:

0.0447

Gnomad4 OTH exome

AF:

0.0435

GnomAD4 genome

AF:

0.0398

AC:

6062

AN:

152266

Hom.:

125

Cov.:

AF XY:

0.0391

AC XY:

2911

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.0469

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.0379

Gnomad4 SAS

AF:

0.0560

Gnomad4 FIN

AF:

0.0307

Gnomad4 NFE

AF:

0.0454

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0452

Hom.:

240

Bravo

AF:

0.0400

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

EpiCase

AF:

0.0455

EpiControl

AF:

0.0481

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.9

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over