rs11039159

Positions:

• chr11-47272470-G-T

Variant summary

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

The ENST00000706887.1(MADD):​c.-88-1357G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,192 control chromosomes in the GnomAD database, including 6,889 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 0.27 (6879 hom., cov: 31)
  • Exomes 𝑓: 0.30 (10 hom.)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADD	NM_001376571.1	c.-88-1357G>T		intron_variant		ENST00000706887.1	NP_001363500.1
MADD	NR_164835.1	n.115-1357G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1	c.-88-1357G>T		intron_variant			NM_001376571.1	ENSP00000516604

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41184 AN: 151908 Hom.: 6883 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.301 AC: 50 AN: 166 Hom.: 10 AF XY: 0.281 AC XY: 32 AN XY: 114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.271 AC: 41178 AN: 152026 Hom.: 6879 Cov.: 31 AF XY: 0.265 AC XY: 19673 AN XY: 74314

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.304

Alfa AF: 0.329 Hom.: 2003

Bravo AF: 0.258

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.59

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: rs11039159; hg19: chr11-47294021;