rs1690916

Positions:

• chr12-68841626-G-A
• chr12-68841626-G-C

Variant summary

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

The NM_002392.6(MDM2):​c.*1777G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 209,294 control chromosomes in the GnomAD database, including 13,628 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 0.35 (9809 hom., cov: 32)
  • Exomes 𝑓: 0.35 (3819 hom.)
• Consequence: MDM2 NM_002392.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570

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]

ENSG00000257181 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDM2	NM_002392.6	c.*1777G>A		3_prime_UTR_variant	11/11	ENST00000258149.11	NP_002383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11	c.*1777G>A		3_prime_UTR_variant	11/11	1	NM_002392.6	ENSP00000258149.6
ENSG00000257181	ENST00000553141.1	n.447C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52691 AN: 151814 Hom.: 9805 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.353 AC: 20245 AN: 57362 Hom.: 3819 Cov.: 0 AF XY: 0.352 AC XY: 9313 AN XY: 26484

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.571

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.347 AC: 52729 AN: 151932 Hom.: 9809 Cov.: 32 AF XY: 0.344 AC XY: 25568 AN XY: 74248

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.335

Alfa AF: 0.388 Hom.: 2833

Bravo AF: 0.329

Asia WGS AF: 0.284 AC: 985 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.45

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: rs1690916; hg19: chr12-69235406;