rs1449626

chr11-47269208-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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]

ACMG classification

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	UniProt
MADD	NM_001376651.1	c.-164A>C		5_prime_UTR_variant	1/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MADD	ENST00000453571.5	c.-164A>C		5_prime_UTR_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40221 AN: 152004 Hom.: 6358 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.191 AC: 357 AN: 1866 Hom.: 41 Cov.: 0 AF XY: 0.207 AC XY: 226 AN XY: 1092

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.312

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.264 AC: 40236 AN: 152122 Hom.: 6361 Cov.: 32 AF XY: 0.273 AC XY: 20284 AN XY: 74366

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.217

Alfa AF: 0.219 Hom.: 1317

Bravo AF: 0.270

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.9
Dann	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1449626; hg19: chr11-47290759;