rs8141025

Positions:

• chr22-35429464-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM5	XM_006724242.5	c.2103+6123A>T		intron_variant			XP_006724305.1
MCM5	XM_047441366.1	c.2103+6123A>T		intron_variant			XP_047297322.1
		n.35429464A>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00602

Gnomad4 FIN AF: 0.00161

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0797

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8141025; hg19: chr22-35825457;