rs749067

chr11-47296606-T-C

Variant summary

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

The ENST00000706887.1(MADD):c.3759+551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,038 control chromosomes in the GnomAD database, including 6,801 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 0.26 (6801 hom., cov: 31)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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 (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MADD	NM_001376571.1	c.3759+551T>C		intron_variant		ENST00000706887.1
MADD	NR_164835.1	n.3949+551T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MADD	ENST00000706887.1	c.3759+551T>C		intron_variant			NM_001376571.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39796 AN: 151920 Hom.: 6805 Cov.: 31

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.262 AC: 39783 AN: 152038 Hom.: 6801 Cov.: 31 AF XY: 0.256 AC XY: 19035 AN XY: 74306

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.297

Alfa AF: 0.368 Hom.: 14552

Bravo AF: 0.247

Asia WGS AF: 0.133 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.5
Dann	Benign	0.73

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: rs749067; hg19: chr11-47318157;