rs1196333

Variant names:

• chr12-68808835-T-A
• rs1196333
• NM_002392.6:c.14+344T>A

Variant summary

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

The NM_002392.6(MDM2):​c.14+344T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 844,256 control chromosomes in the GnomAD database, including 527 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 0.045 (327 hom., cov: 33)
  • Exomes 𝑓: 0.017 (200 hom.)
• Consequence: MDM2 NM_002392.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDM2	NM_002392.6	c.14+344T>A		intron_variant	Intron 1 of 10	ENST00000258149.11	NP_002383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11	c.14+344T>A		intron_variant	Intron 1 of 10	1	NM_002392.6	ENSP00000258149.6

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6895 AN: 152158 Hom.: 326 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0174 AC: 12027 AN: 691980 Hom.: 200 AF XY: 0.0173 AC XY: 5560 AN XY: 321930

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.00998

Gnomad4 ASJ exome AF: 0.00594

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00488

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0455 AC: 6924 AN: 152276 Hom.: 327 Cov.: 33 AF XY: 0.0445 AC XY: 3316 AN XY: 74470

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.0331

Alfa AF: 0.0334 Hom.: 29

Bravo AF: 0.0500

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.88
DANN	Benign	0.74
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1196333; hg19: chr12-69202615;