dbSNP rs4245739: MDM4:c.*32C>A (chr1-204549714-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002393.5(MDM4):c.*32C>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 0.75 in 1,210,462 control chromosomes in the GnomAD database, including 341,577 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 0.76 ( 44023 hom., cov: 33)

Exomes 𝑓: 0.75 ( 297554 hom. )

Consequence

MDM4
NM_002393.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.135

Variant links:

Genes affected

MDM4 (HGNC:6974): (MDM4 regulator of p53) This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2011]

MDM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDM4	NM_002393.5 link	c.*32C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000367182.8	NP_002384.2	O15151-1Q59FS6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDM4	ENST00000367182.8 link	c.*32C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_002393.5	ENSP00000356150.3		O15151-1

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115311

AN:

152058

Hom.:

44003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.961

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.866

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.733

Gnomad OTH

AF:

0.734

GnomAD3 exomes

AF:

0.772

AC:

124143

AN:

160836

Hom.:

48323

AF XY:

0.767

AC XY:

66907

AN XY:

87178

show subpopulations

Gnomad AFR exome

AF:

0.769

Gnomad AMR exome

AF:

0.759

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.970

Gnomad SAS exome

AF:

0.744

Gnomad FIN exome

AF:

0.856

Gnomad NFE exome

AF:

0.733

Gnomad OTH exome

AF:

0.740

GnomAD4 exome

AF:

0.748

AC:

792101

AN:

1058286

Hom.:

297554

Cov.:

AF XY:

0.748

AC XY:

394976

AN XY:

528202

show subpopulations

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.753

Gnomad4 ASJ exome

AF:

0.699

Gnomad4 EAS exome

AF:

0.963

Gnomad4 SAS exome

AF:

0.748

Gnomad4 FIN exome

AF:

0.839

Gnomad4 NFE exome

AF:

0.734

Gnomad4 OTH exome

AF:

0.747

GnomAD4 genome

AF:

0.758

AC:

115383

AN:

152176

Hom.:

44023

Cov.:

AF XY:

0.765

AC XY:

56886

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.764

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.962

Gnomad4 SAS

AF:

0.752

Gnomad4 FIN

AF:

0.866

Gnomad4 NFE

AF:

0.733

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.728

Hom.:

50343

Bravo

AF:

0.749

Asia WGS

AF:

0.805

AC:

2798

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.41

DANN

Benign

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over