chr11-47274644-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The ENST00000706887.1(MADD):c.144G>A(p.Leu48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,614,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 1 hom. )
Consequence
MADD
ENST00000706887.1 synonymous
ENST00000706887.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.722
Genes affected
MADD (HGNC:6766): (MAP kinase activating death domain) Tumor necrosis factor alpha (TNF-alpha) is a signaling molecule that interacts with one of two receptors on cells targeted for apoptosis. The apoptotic signal is transduced inside these cells by cytoplasmic adaptor proteins. The protein encoded by this gene is a death domain-containing adaptor protein that interacts with the death domain of TNF-alpha receptor 1 to activate mitogen-activated protein kinase (MAPK) and propagate the apoptotic signal. It is membrane-bound and expressed at a higher level in neoplastic cells than in normal cells. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 11-47274644-G-A is Benign according to our data. Variant chr11-47274644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641760.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MADD | NM_001376571.1 | c.144G>A | p.Leu48= | synonymous_variant | 3/37 | ENST00000706887.1 | |
MADD | NR_164835.1 | n.346G>A | non_coding_transcript_exon_variant | 3/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MADD | ENST00000706887.1 | c.144G>A | p.Leu48= | synonymous_variant | 3/37 | NM_001376571.1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251398Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135888
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GnomAD4 exome AF: 0.000166 AC: 242AN: 1461870Hom.: 1 Cov.: 32 AF XY: 0.000177 AC XY: 129AN XY: 727234
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10AN XY: 74348
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | MADD: BP4, BP7 - |
Computational scores
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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