rs1690916

Variant names:

• chr12-68841626-G-A
• rs1690916
• NM_002392.6:c.*1777G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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)

ENSG00000257181 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.*1777G>A		3_prime_UTR	Exon 11 of 11	NP_002383.2	Q00987-11
	MDM2	NM_001367990.1		c.*1777G>A		3_prime_UTR	Exon 11 of 11	NP_001354919.1	Q00987-1
	MDM2	NM_001145337.3		c.*1777G>A		3_prime_UTR	Exon 11 of 11	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.*1777G>A		3_prime_UTR	Exon 11 of 11	ENSP00000258149.6	Q00987-11
	MDM2	ENST00000951805.1		c.*1777G>A		3_prime_UTR	Exon 11 of 11	ENSP00000621864.1
	ENSG00000257181	ENST00000553141.1	TSL:3	n.447C>T		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.257 AC: 648 AN: 2520

American (AMR) AF: 0.238 AC: 397 AN: 1666

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 900 AN: 3672

East Asian (EAS) AF: 0.279 AC: 2410 AN: 8626

South Asian (SAS) AF: 0.209 AC: 111 AN: 530

European-Finnish (FIN) AF: 0.571 AC: 24 AN: 42

Middle Eastern (MID) AF: 0.255 AC: 94 AN: 368

European-Non Finnish (NFE) AF: 0.399 AC: 14084 AN: 35278

Other (OTH) AF: 0.338 AC: 1577 AN: 4660

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

African (AFR) AF: 0.260 AC: 10764 AN: 41428

American (AMR) AF: 0.244 AC: 3720 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 906 AN: 3464

East Asian (EAS) AF: 0.281 AC: 1454 AN: 5166

South Asian (SAS) AF: 0.247 AC: 1190 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4678 AN: 10522

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28760 AN: 67952

Other (OTH) AF: 0.335 AC: 705 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.45
PhyloP100		0.57
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: rs1690916; hg19: chr12-69235406;