rs4752979

Positions:

• chr11-47317629-A-G

Variant summary

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

The NM_001376571.1(MADD):​c.4377+2302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,836 control chromosomes in the GnomAD database, including 8,745 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 0.31 (8745 hom., cov: 31)
• Consequence: MADD NM_001376571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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]

MADD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADD	NM_001376571.1	c.4377+2302A>G		intron_variant			NP_001363500.1
MADD	NM_003682.4	c.4377+2302A>G		intron_variant			NP_003673.3
MADD	NM_001376572.1	c.4365+2302A>G		intron_variant			NP_001363501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1	c.4377+2302A>G		intron_variant				ENSP00000516604.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47793 AN: 151718 Hom.: 8746 Cov.: 31

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 47821 AN: 151836 Hom.: 8745 Cov.: 31 AF XY: 0.325 AC XY: 24079 AN XY: 74186

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.264

Alfa AF: 0.222 Hom.: 5745

Bravo AF: 0.317

Asia WGS AF: 0.451 AC: 1567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.51

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: rs4752979; hg19: chr11-47339180;