chr1-204549118-G-A
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002393.5(MDM4):c.909G>A(p.Glu303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,592,810 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0036 ( 14 hom., cov: 33)
Exomes 𝑓: 0.0021 ( 100 hom. )
Consequence
MDM4
NM_002393.5 synonymous
NM_002393.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.428
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 1-204549118-G-A is Benign according to our data. Variant chr1-204549118-G-A is described in ClinVar as [Benign]. Clinvar id is 770500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.428 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDM4 | NM_002393.5 | c.909G>A | p.Glu303= | synonymous_variant | 11/11 | ENST00000367182.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDM4 | ENST00000367182.8 | c.909G>A | p.Glu303= | synonymous_variant | 11/11 | 1 | NM_002393.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00359 AC: 546AN: 152176Hom.: 14 Cov.: 33
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GnomAD3 exomes AF: 0.00984 AC: 2365AN: 240306Hom.: 82 AF XY: 0.00712 AC XY: 924AN XY: 129798
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GnomAD4 exome AF: 0.00205 AC: 2959AN: 1440516Hom.: 100 Cov.: 29 AF XY: 0.00169 AC XY: 1211AN XY: 716478
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GnomAD4 genome AF: 0.00359 AC: 547AN: 152294Hom.: 14 Cov.: 33 AF XY: 0.00416 AC XY: 310AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at