rs7944584

Positions:

• chr11-47314769-A-T

Variant summary

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

The ENST00000706887.1(MADD):​c.4270-451A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,248 control chromosomes in the GnomAD database, including 3,494 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 0.19 (3494 hom., cov: 32)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MADD	NM_001376571.1	c.4270-451A>T		intron_variant		ENST00000706887.1
MADD	NR_164835.1	n.4460-451A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MADD	ENST00000706887.1	c.4270-451A>T		intron_variant			NM_001376571.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28329 AN: 152130 Hom.: 3495 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.186 AC: 28324 AN: 152248 Hom.: 3494 Cov.: 32 AF XY: 0.181 AC XY: 13435 AN XY: 74428

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.222

Alfa AF: 0.256 Hom.: 2992

Bravo AF: 0.179

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
DANN	Benign	0.63

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: rs7944584; hg19: chr11-47336320;