rs11039183

Positions:

• chr11-47325389-G-A

Variant summary

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

The ENST00000706887.1(MADD):​c.4722+812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,506 control chromosomes in the GnomAD database, including 6,077 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 0.25 (6047 hom., cov: 31)
  • Exomes 𝑓: 0.31 (30 hom.)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADD	NM_001376571.1	c.4722+812G>A		intron_variant		ENST00000706887.1	NP_001363500.1
MADD	NR_164835.1	n.4984+56G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1	c.4722+812G>A		intron_variant			NM_001376571.1	ENSP00000516604

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38676 AN: 151886 Hom.: 6049 Cov.: 31

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.309 AC: 155 AN: 502 Hom.: 30 AF XY: 0.316 AC XY: 98 AN XY: 310

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.254 AC: 38676 AN: 152004 Hom.: 6047 Cov.: 31 AF XY: 0.249 AC XY: 18496 AN XY: 74302

Gnomad4 AFR AF: 0.0969

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0213

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.281

Alfa AF: 0.318 Hom.: 1992

Bravo AF: 0.241

Asia WGS AF: 0.128 AC: 447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11039183; hg19: chr11-47346940;