rs8141025

Variant names:

• chr22-35429464-A-T
• rs8141025
• XM_006724242.5:c.2103+6123A>T

Variant summary

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

The XM_006724242.5(MCM5):​c.2103+6123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 151,922 control chromosomes in the GnomAD database, including 2,316 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 0.10 (2316 hom., cov: 31)
• Consequence: MCM5 XM_006724242.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 3 publications found

Genes affected

MCM5 (HGNC:6948): (minichromosome maintenance complex component 5) The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation. [provided by RefSeq, Jul 2008]

MCM5 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 8

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15801 AN: 151810 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00623

Gnomad FIN AF: 0.00161

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15816 AN: 151922 Hom.: 2316 Cov.: 31 AF XY: 0.101 AC XY: 7468 AN XY: 74252

African (AFR) AF: 0.328 AC: 13570 AN: 41378

American (AMR) AF: 0.0458 AC: 698 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00602 AC: 29 AN: 4814

European-Finnish (FIN) AF: 0.00161 AC: 17 AN: 10546

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0168 AC: 1144 AN: 67978

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0670 Hom.: 184

Bravo AF: 0.118

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8141025; hg19: chr22-35825457;