rs10501320

Positions:

• chr11-47272248-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000706887.1(MADD):​c.-88-1579G>C variant causes a intron change. The variant allele was found at a frequency of 0.173 in 152,150 control chromosomes in the GnomAD database, including 3,064 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 0.17 (3064 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADD	NM_001376571.1	c.-88-1579G>C		intron_variant		ENST00000706887.1	NP_001363500.1
MADD	NR_164835.1	n.115-1579G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1	c.-88-1579G>C		intron_variant			NM_001376571.1	ENSP00000516604

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26280 AN: 152028 Hom.: 3065 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.173 AC: 26277 AN: 152146 Hom.: 3064 Cov.: 32 AF XY: 0.166 AC XY: 12342 AN XY: 74380

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0822

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.209

Alfa AF: 0.216 Hom.: 505

Bravo AF: 0.168

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.93

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: rs10501320; hg19: chr11-47293799;