rs1449626
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001376651.1(MADD):c.-164A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 153,988 control chromosomes in the GnomAD database, including 6,402 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 0.26 ( 6361 hom., cov: 32)
Exomes 𝑓: 0.19 ( 41 hom. )
Consequence
MADD
NM_001376651.1 5_prime_UTR
NM_001376651.1 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.122
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MADD | NM_001376651.1 | c.-164A>C | 5_prime_UTR_variant | 1/33 | NP_001363580.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MADD | ENST00000453571.5 | c.-164A>C | 5_prime_UTR_variant | 1/3 | 4 | ENSP00000388255 |
Frequencies
GnomAD3 genomes AF: 0.265 AC: 40221AN: 152004Hom.: 6358 Cov.: 32
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GnomAD4 exome AF: 0.191 AC: 357AN: 1866Hom.: 41 Cov.: 0 AF XY: 0.207 AC XY: 226AN XY: 1092
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GnomAD4 genome AF: 0.264 AC: 40236AN: 152122Hom.: 6361 Cov.: 32 AF XY: 0.273 AC XY: 20284AN XY: 74366
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ClinVar
Not reported inComputational scores
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Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at