rs1470383

Positions:

• chr12-68813382-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002392.6(MDM2):​c.100-172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,228 control chromosomes in the GnomAD database, including 59,275 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 0.88 (59275 hom., cov: 32)
• Consequence: MDM2 NM_002392.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

Genes affected

MDM2 (HGNC:6973): (MDM2 proto-oncogene) This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDM2	NM_002392.6	c.100-172G>A		intron_variant		ENST00000258149.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDM2	ENST00000258149.11	c.100-172G>A		intron_variant		1	NM_002392.6

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133918 AN: 152112 Hom.: 59214 Cov.: 32

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.866

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

GnomAD4 genome AF: 0.880 AC: 134036 AN: 152228 Hom.: 59275 Cov.: 32 AF XY: 0.880 AC XY: 65452 AN XY: 74404

Gnomad4 AFR AF: 0.969

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.864

Alfa AF: 0.848 Hom.: 86896

Bravo AF: 0.884

Asia WGS AF: 0.842 AC: 2925 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.24

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: rs1470383; hg19: chr12-69207162;