11-47278878-T-C

Position:

• chr11-47278878-T-C

Variant summary

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

The ENST00000706887.1(MADD):​c.1210-121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 717,986 control chromosomes in the GnomAD database, including 25,644 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 0.28 (7400 hom., cov: 32)
  • Exomes 𝑓: 0.22 (18244 hom.)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADD	NM_001376571.1	c.1210-121T>C		intron_variant		ENST00000706887.1	NP_001363500.1
MADD	NR_164835.1	n.1412-121T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1	c.1210-121T>C		intron_variant			NM_001376571.1	ENSP00000516604

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42719 AN: 151978 Hom.: 7394 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.224 AC: 126801 AN: 565890 Hom.: 18244 AF XY: 0.222 AC XY: 66629 AN XY: 300268

Gnomad4 AFR exome AF: 0.432

Gnomad4 AMR exome AF: 0.355

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.281 AC: 42751 AN: 152096 Hom.: 7400 Cov.: 32 AF XY: 0.289 AC XY: 21494 AN XY: 74358

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.230

Alfa AF: 0.207 Hom.: 755

Bravo AF: 0.289

Asia WGS AF: 0.334 AC: 1157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.81
DANN	Benign	0.39

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

Other links and lift over

dbSNP: rs4752977; hg19: chr11-47300429;