Genetic Variant MCM7:p.Ala480Ala (chr7-100095929-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

20 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MCM7	NM_005916.5 link	c.1440C>T	p.Ala480Ala	synonymous_variant	Exon 11 of 15	ENST00000303887.10	NP_005907.3	P33993-1C6EMX8A0A0S2Z4A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM7	ENST00000303887.10 link	c.1440C>T	p.Ala480Ala	synonymous_variant	Exon 11 of 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

GnomAD2 exomes

AF:

0.0419

AC:

10521

AN:

251218

AF XY:

0.0424

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 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

African (AFR)

AF:

0.0289

AC:

967

AN:

33478

American (AMR)

AF:

0.0324

AC:

1451

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0328

AC:

856

AN:

26136

East Asian (EAS)

AF:

0.0421

AC:

1673

AN:

39698

South Asian (SAS)

AF:

0.0508

AC:

4381

AN:

86250

European-Finnish (FIN)

AF:

0.0374

AC:

1993

AN:

53298

Middle Eastern (MID)

AF:

0.0548

AC:

316

AN:

5766

European-Non Finnish (NFE)

AF:

0.0447

AC:

49729

AN:

1111962

Other (OTH)

AF:

0.0435

AC:

2625

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3926

7853

11779

15706

19632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1838

3676

5514

7352

9190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0398

AC:

6062

AN:

152266

Hom.:

125

Cov.:

AF XY:

0.0391

AC XY:

2911

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0292

AC:

1213

AN:

41554

American (AMR)

AF:

0.0469

AC:

717

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3472

East Asian (EAS)

AF:

0.0379

AC:

196

AN:

5176

South Asian (SAS)

AF:

0.0560

AC:

270

AN:

4820

European-Finnish (FIN)

AF:

0.0307

AC:

326

AN:

10620

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0454

AC:

3089

AN:

68008

Other (OTH)

AF:

0.0440

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

306

611

917

1222

1528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0443

Hom.:

306

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

(source)

DANN

Benign

0.87

PhyloP100

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over