chr11-47328736-G-A

Position:

• chr11-47328736-G-A

Variant summary

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

The ENST00000706887.1(MADD):​c.4848+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,942 control chromosomes in the GnomAD database, including 72,370 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 0.34 (9765 hom., cov: 33)
  • Exomes 𝑓: 0.28 (62605 hom.)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MADD	NM_001376571.1	c.4848+32G>A		intron_variant		ENST00000706887.1
MADD	NR_164835.1	n.5101+32G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MADD	ENST00000706887.1	c.4848+32G>A		intron_variant			NM_001376571.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51798 AN: 152052 Hom.: 9760 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.312

GnomAD3 exomes AF: 0.339 AC: 84608 AN: 249558 Hom.: 16227 AF XY: 0.330 AC XY: 44540 AN XY: 134906

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.433

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.650

Gnomad SAS exome AF: 0.363

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.279 AC: 408180 AN: 1460772 Hom.: 62605 Cov.: 36 AF XY: 0.281 AC XY: 203866 AN XY: 726652

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.637

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.341 AC: 51837 AN: 152170 Hom.: 9765 Cov.: 33 AF XY: 0.349 AC XY: 25976 AN XY: 74404

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.308

Alfa AF: 0.231 Hom.: 954

Bravo AF: 0.346

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2305280; hg19: chr11-47350287; COSMIC: COSV57024912; COSMIC: COSV57024912;