rs1470383

Variant names:

• chr12-68813382-G-A
• rs1470383
• NM_002392.6:c.100-172G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-68813382-G-A
• chr12-68813382-G-C
• chr12-68813382-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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]

MDM2 Gene-Disease associations (from GenCC):

• Li-Fraumeni syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lessel-kubisch syndrome

  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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002392.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDM2	NM_002392.6	MANE Select	c.100-172G>A		intron	N/A	NP_002383.2	Q00987-11
	MDM2	NM_001367990.1		c.82-172G>A		intron	N/A	NP_001354919.1	Q00987-1
	MDM2	NM_001145337.3		c.82-172G>A		intron	N/A	NP_001138809.1	A0A0A8KB75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDM2	ENST00000258149.11	TSL:1 MANE Select	c.100-172G>A		intron	N/A	ENSP00000258149.6	Q00987-11
	MDM2	ENST00000539479.6	TSL:1	c.82-172G>A		intron	N/A	ENSP00000444430.2	Q00987-1
	MDM2	ENST00000350057.9	TSL:1	c.82-3430G>A		intron	N/A	ENSP00000266624.9	J3KN53

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

African (AFR) AF: 0.969 AC: 40284 AN: 41582

American (AMR) AF: 0.858 AC: 13096 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2927 AN: 3472

East Asian (EAS) AF: 0.831 AC: 4307 AN: 5184

South Asian (SAS) AF: 0.850 AC: 4095 AN: 4820

European-Finnish (FIN) AF: 0.881 AC: 9332 AN: 10590

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.841 AC: 57173 AN: 68002

Other (OTH) AF: 0.864 AC: 1825 AN: 2112

Alfa AF: 0.857 Hom.: 161989

Bravo AF: 0.884

Asia WGS AF: 0.842 AC: 2925 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.24
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1470383; hg19: chr12-69207162;