chr7-100099174-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM7	NM_005916.5	c.431A>G	p.Asn144Ser	missense_variant	Exon 5 of 15	ENST00000303887.10	NP_005907.3
MCM7	XM_005250348.4	c.110A>G	p.Asn37Ser	missense_variant	Exon 5 of 15		XP_005250405.1
MCM7	NM_001278595.2	c.-98A>G		5_prime_UTR_variant	Exon 4 of 14		NP_001265524.1
MCM7	NM_182776.3	c.-98A>G		5_prime_UTR_variant	Exon 4 of 14		NP_877577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM7	ENST00000303887.10	c.431A>G	p.Asn144Ser	missense_variant	Exon 5 of 15	1	NM_005916.5	ENSP00000307288.5

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

GnomAD3 exomes AF: 0.239 AC: 60161 AN: 251466 Hom.: 7802 AF XY: 0.245 AC XY: 33237 AN XY: 135914

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 SAS exome AF: 0.231

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

Gnomad4 AFR exome AF: 0.0424

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.247

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

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.199

Alfa AF: 0.258 Hom.: 13109

Bravo AF: 0.187

TwinsUK AF: 0.299 AC: 1110

ALSPAC AF: 0.276 AC: 1065

ESP6500AA AF: 0.0651 AC: 287

ESP6500EA AF: 0.286 AC: 2459

ExAC AF: 0.238 AC: 28943

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 v4.3

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;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.61	T;T;T
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N;N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.84	N;N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.75	T;T;.
Polyphen		0.0	.;B;.
Vest4		0.082
MPC		0.10
ClinPred		0.0010	T
GERP RS		-3.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.086
gMVP		0.21

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

Other links and lift over

dbSNP: rs2070215; hg19: chr7-99696797; COSMIC: COSV57994689; COSMIC: COSV57994689;