chr7-100095929-G-A

Variant names:

• chr7-100095929-G-A
• rs2307355
• NM_005916.5:c.1440C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 20 publications found

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]

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM7	NM_005916.5	MANE Select	c.1440C>T	p.Ala480Ala	synonymous	Exon 11 of 15	NP_005907.3
	MCM7	NM_001439271.1		c.1119C>T	p.Ala373Ala	synonymous	Exon 11 of 15	NP_001426200.1
	MCM7	NM_001439272.1		c.1119C>T	p.Ala373Ala	synonymous	Exon 11 of 15	NP_001426201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM7	ENST00000303887.10	TSL:1 MANE Select	c.1440C>T	p.Ala480Ala	synonymous	Exon 11 of 15	ENSP00000307288.5	P33993-1
	MCM7	ENST00000343023.10	TSL:1	c.985+1905C>T		intron	N/A	ENSP00000344006.6	P33993-2
	MCM7	ENST00000489841.6	TSL:1	n.2161C>T		non_coding_transcript_exon	Exon 10 of 14

Frequencies

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

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

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.: 33 AF XY: 0.0440 AC XY: 31983 AN XY: 727148

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

GnomAD4 genome AF: 0.0398 AC: 6062 AN: 152266 Hom.: 125 Cov.: 32 AF XY: 0.0391 AC XY: 2911 AN XY: 74454

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: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0454 AC: 3089 AN: 68008

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.9
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)

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

Other links and lift over

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