rs2070215

Variant names:

• chr7-100099174-T-C
• rs2070215
• NM_005916.5:c.431A>G
• MCM7 p.Asn144Ser

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005916.5(MCM7):​c.431A>G​(p.Asn144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,792 control chromosomes in the GnomAD database, including 57,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3891 hom., cov: 30)
  • Exomes 𝑓: 0.27 (54102 hom.)
• Consequence: MCM7 NM_005916.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440
• Publications: 54 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021751225).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.272 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.431A>G	p.Asn144Ser	missense	Exon 5 of 15	NP_005907.3
	MCM7	NM_001439271.1		c.110A>G	p.Asn37Ser	missense	Exon 5 of 15	NP_001426200.1
	MCM7	NM_001439272.1		c.110A>G	p.Asn37Ser	missense	Exon 5 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.431A>G	p.Asn144Ser	missense	Exon 5 of 15	ENSP00000307288.5	P33993-1
	MCM7	ENST00000343023.10	TSL:1	c.431A>G	p.Asn144Ser	missense	Exon 5 of 9	ENSP00000344006.6	P33993-2
	MCM7	ENST00000489841.6	TSL:1	n.1152A>G		non_coding_transcript_exon	Exon 4 of 14

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30788 AN: 151882 Hom.: 3889 Cov.: 30

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.239 AC: 60161 AN: 251466 AF XY: 0.245

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.164

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.260

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.276

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.267 AC: 390920 AN: 1461792 Hom.: 54102 Cov.: 48 AF XY: 0.267 AC XY: 193993 AN XY: 727196

African (AFR) AF: 0.0424 AC: 1421 AN: 33480

American (AMR) AF: 0.164 AC: 7344 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6434 AN: 26136

East Asian (EAS) AF: 0.264 AC: 10467 AN: 39700

South Asian (SAS) AF: 0.234 AC: 20215 AN: 86256

European-Finnish (FIN) AF: 0.296 AC: 15808 AN: 53416

Middle Eastern (MID) AF: 0.146 AC: 841 AN: 5768

European-Non Finnish (NFE) AF: 0.282 AC: 313494 AN: 1111920

Other (OTH) AF: 0.247 AC: 14896 AN: 60392

GnomAD4 genome AF: 0.203 AC: 30793 AN: 152000 Hom.: 3891 Cov.: 30 AF XY: 0.203 AC XY: 15097 AN XY: 74284

African (AFR) AF: 0.0545 AC: 2263 AN: 41498

American (AMR) AF: 0.173 AC: 2644 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1388 AN: 5154

South Asian (SAS) AF: 0.247 AC: 1189 AN: 4818

European-Finnish (FIN) AF: 0.295 AC: 3113 AN: 10556

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18679 AN: 67936

Other (OTH) AF: 0.199 AC: 417 AN: 2100

Alfa AF: 0.250 Hom.: 16594

Bravo AF: 0.187

Asia WGS AF: 0.277 AC: 967 AN: 3478

EpiCase AF: 0.266

EpiControl AF: 0.273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.66
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.044
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.086
gMVP		0.21
Mutation Taster		=297/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2070215;

hg19: chr7-99696797;

COSMIC: COSV57994689;

COSMIC: COSV57994689;