rs1201644

Positions:

• chr12-68820911-G-A
• chr12-68820911-G-T

Variant summary

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

The ENST00000258149.11(MDM2):​c.358+537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,948 control chromosomes in the GnomAD database, including 23,115 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 0.53 (23115 hom., cov: 32)
• Consequence: MDM2 ENST00000258149.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDM2	NM_002392.6	c.358+537G>A		intron_variant		ENST00000258149.11	NP_002383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11	c.358+537G>A		intron_variant		1	NM_002392.6	ENSP00000258149

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80387 AN: 151832 Hom.: 23072 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.530 AC: 80495 AN: 151948 Hom.: 23115 Cov.: 32 AF XY: 0.520 AC XY: 38633 AN XY: 74260

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.481

Alfa AF: 0.503 Hom.: 4201

Bravo AF: 0.534

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.17

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: rs1201644; hg19: chr12-69214691;