chr7-100094248-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005916.5(MCM7):c.1773G>C(p.Glu591Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,204 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 8 hom. )

Consequence

MCM7
NM_005916.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.78

Publications

4 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:

MIR106B (HGNC:31495): (microRNA 106b) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR106B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011098564).

BP6

Variant 7-100094248-C-G is Benign according to our data. Variant chr7-100094248-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 774658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 322 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005916.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MCM7	NM_005916.5	MANE Select	c.1773G>C	p.Glu591Asp	missense	Exon 13 of 15	NP_005907.3
MCM7	NM_001439271.1		c.1452G>C	p.Glu484Asp	missense	Exon 13 of 15	NP_001426200.1
MCM7	NM_001439272.1		c.1452G>C	p.Glu484Asp	missense	Exon 13 of 15	NP_001426201.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MCM7	ENST00000303887.10	TSL:1 MANE Select	c.1773G>C	p.Glu591Asp	missense	Exon 13 of 15	ENSP00000307288.5	P33993-1
MCM7	ENST00000343023.10	TSL:1	c.986-1132G>C		intron	N/A	ENSP00000344006.6	P33993-2
MCM7	ENST00000489841.6	TSL:1	n.2494G>C		non_coding_transcript_exon	Exon 12 of 14

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00315

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00199

AC:

501

AN:

251480

AF XY:

0.00198

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00349

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00320

AC:

4684

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

2269

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33480

American (AMR)

AF:

0.00181

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000786

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00387

AC:

4307

AN:

1112010

Other (OTH)

AF:

0.00316

AC:

191

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

267

535

802

1070

1337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.00211

AC:

322

AN:

152314

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41566

American (AMR)

AF:

0.00346

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00315

AC:

214

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00252

Hom.:

Bravo

AF:

0.00234

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MCM7-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.045

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.59

PhyloP100

1.8

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.75

REVEL

Benign

0.21

Sift

Benign

0.54

Sift4G

Benign

0.37

Polyphen

0.0080

Vest4

0.74

MutPred

0.53

Loss of catalytic residue at W593 (P = 0.0318)

MVP

0.22

MPC

0.14

ClinPred

0.0074

GERP RS

2.2

Varity_R

0.26

gMVP

0.44

Mutation Taster

=87/13

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over