rs2307355

Variant summary

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

The ENST00000303887.10(MCM7):​c.1440C>T​(p.Ala480=) 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
ENST00000303887.10 synonymous

Scores

2

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]

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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
MCM7NM_005916.5 linkuse as main transcriptc.1440C>T p.Ala480= synonymous_variant 11/15 ENST00000303887.10 NP_005907.3
MCM7NM_001278595.2 linkuse as main transcriptc.912C>T p.Ala304= synonymous_variant 10/14 NP_001265524.1
MCM7NM_182776.3 linkuse as main transcriptc.912C>T p.Ala304= synonymous_variant 10/14 NP_877577.1
MCM7XM_005250348.4 linkuse as main transcriptc.1119C>T p.Ala373= synonymous_variant 11/15 XP_005250405.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MCM7ENST00000303887.10 linkuse as main transcriptc.1440C>T p.Ala480= synonymous_variant 11/151 NM_005916.5 ENSP00000307288 P1P33993-1

Frequencies

GnomAD3 genomes
AF:
0.0398
AC:
6060
AN:
152148
Hom.:
125
Cov.:
32
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.:
33
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.:
32
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.

Other links and lift over

dbSNP: rs2307355; hg19: chr7-99693552; COSMIC: COSV57999369; COSMIC: COSV57999369; API