7-100093384-C-T

Variant names:

• chr7-100093384-C-T
• rs2307349
• NM_005916.5:c.1866G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005916.5(MCM7):​c.1866G>A​(p.Val622Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,614,080 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (228 hom., cov: 33)
  • Exomes 𝑓: 0.0031 (240 hom.)
• Consequence: MCM7 NM_005916.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.424

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]

MIR25 (HGNC:31609): (microRNA 25) 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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 7-100093384-C-T is Benign according to our data. Variant chr7-100093384-C-T is described in ClinVar as [Benign]. Clinvar id is 768184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.424 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM7	NM_005916.5	c.1866G>A	p.Val622Val	synonymous_variant	Exon 14 of 15	ENST00000303887.10	NP_005907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM7	ENST00000303887.10	c.1866G>A	p.Val622Val	synonymous_variant	Exon 14 of 15	1	NM_005916.5	ENSP00000307288.5

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4525 AN: 152164 Hom.: 227 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00790 AC: 1987 AN: 251440 Hom.: 99 AF XY: 0.00580 AC XY: 788 AN XY: 135892

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.00607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000272

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00307 AC: 4483 AN: 1461798 Hom.: 240 Cov.: 31 AF XY: 0.00267 AC XY: 1938 AN XY: 727202

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000196

Gnomad4 OTH exome AF: 0.00689

GnomAD4 genome AF: 0.0298 AC: 4537 AN: 152282 Hom.: 228 Cov.: 33 AF XY: 0.0282 AC XY: 2097 AN XY: 74460

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00749 Hom.: 46

Bravo AF: 0.0334

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.8
DANN	Benign	0.79
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

Other links and lift over

dbSNP: rs2307349; hg19: chr7-99691007;