Variant rs1795480 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000258149.11(MDM2):c.607C>T(p.Leu203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,613,910 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 35 hom., cov: 32)

Exomes 𝑓: 0.015 ( 190 hom. )

Consequence

MDM2
ENST00000258149.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.63

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-68828854-C-T is Benign according to our data. Variant chr12-68828854-C-T is described in ClinVar as [Benign]. Clinvar id is 472749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0182 (2766/152182) while in subpopulation AFR AF= 0.0282 (1169/41494). AF 95% confidence interval is 0.0268. There are 35 homozygotes in gnomad4. There are 1321 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDM2	NM_002392.6 linkuse as main transcript	c.607C>T	p.Leu203=	synonymous_variant	8/11	ENST00000258149.11	NP_002383.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11 linkuse as main transcript	c.607C>T	p.Leu203=	synonymous_variant	8/11	1	NM_002392.6	ENSP00000258149		Q00987-11

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2760

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.0220

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0163

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0142

AC:

3546

AN:

249424

Hom.:

AF XY:

0.0141

AC XY:

1906

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.00620

Gnomad ASJ exome

AF:

0.00576

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00360

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0148

AC:

21685

AN:

1461728

Hom.:

190

Cov.:

AF XY:

0.0145

AC XY:

10565

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.00704

Gnomad4 ASJ exome

AF:

0.00501

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00405

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0182

AC:

2766

AN:

152182

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1321

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0282

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0220

Gnomad4 NFE

AF:

0.0163

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0185

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0171

EpiControl

AF:

0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Accelerated tumor formation, susceptibility to

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

MDM2-related condition

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 14, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over