11-47271906-C-T

Position:

• chr11-47271906-C-T

Variant summary

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

The ENST00000706887.1(MADD):​c.-89+1660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 152,248 control chromosomes in the GnomAD database, including 185 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 0.042 (185 hom., cov: 32)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: MADD ENST00000706887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946

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-AS1 (HGNC:40354): (MADD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MADD	NM_001376571.1	c.-89+1660C>T		intron_variant		ENST00000706887.1	NP_001363500.1
MADD-AS1	NR_120569.1	n.35+170G>A		intron_variant, non_coding_transcript_variant
MADD	NR_164835.1	n.114+1660C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1	c.-89+1660C>T		intron_variant			NM_001376571.1	ENSP00000516604
MADD-AS1	ENST00000543925.5	n.35+170G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6466 AN: 152114 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0579

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 AF XY: 0.0714 AC XY: 1 AN XY: 14

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0425 AC: 6466 AN: 152232 Hom.: 185 Cov.: 32 AF XY: 0.0435 AC XY: 3240 AN XY: 74398

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0398

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.0579

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0539 Hom.: 355

Bravo AF: 0.0364

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.53

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: rs7114704; hg19: chr11-47293457;