rs937282

Variant names:

• chr12-68808017-C-G
• rs937282
• NM_002392.6:c.-461C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002392.6(MDM2):​c.-461C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,986 control chromosomes in the GnomAD database, including 25,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (25573 hom., cov: 31)
• Consequence: MDM2 NM_002392.6 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-68808017-C-G is Benign according to our data. Variant chr12-68808017-C-G is described in ClinVar as [Benign]. Clinvar id is 1164285.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDM2	NM_002392.6	c.-461C>G		upstream_gene_variant		ENST00000258149.11	NP_002383.2
MDM2	NM_001145339.2	c.-461C>G		upstream_gene_variant			NP_001138811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11	c.-461C>G		upstream_gene_variant		1	NM_002392.6	ENSP00000258149.6
MDM2	ENST00000393412.7	c.-479C>G		upstream_gene_variant		5		ENSP00000377064.4

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83598 AN: 151872 Hom.: 25524 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.551 AC: 83711 AN: 151986 Hom.: 25573 Cov.: 31 AF XY: 0.540 AC XY: 40145 AN XY: 74282

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.497

Alfa AF: 0.537 Hom.: 2949

Bravo AF: 0.558

Asia WGS AF: 0.355 AC: 1230 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Accelerated tumor formation, susceptibility to Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.60
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs937282; hg19: chr12-69201797;