Variant 11-47285079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 8P and 9B. PVS1BP6BA1

The NM_001376571.1(MADD):c.2296C>T(p.Arg766*) variant causes a stop gained change. The variant allele was found at a frequency of 0.052 in 1,614,010 control chromosomes in the GnomAD database, including 2,579 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.039 ( 183 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2396 hom. )

Consequence

MADD
NM_001376571.1 stop_gained

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.27

Variant links:

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 links:

MADD (HGNC:):

MADD links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 11-47285079-C-T is Benign according to our data. Variant chr11-47285079-C-T is described in ClinVar as [Benign]. Clinvar id is 3037635.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
MADD	NM_001376571.1 linkuse as main transcript	c.2296C>T	p.Arg766*	stop_gained	13/37	NP_001363500.1
MADD	NM_003682.4 linkuse as main transcript	c.2296C>T	p.Arg766*	stop_gained	13/36	NP_003673.3	Q8WXG6-1
MADD	NM_001376572.1 linkuse as main transcript	c.2296C>T	p.Arg766*	stop_gained	13/37	NP_001363501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1 linkuse as main transcript	c.2296C>T	p.Arg766*	stop_gained	13/37			ENSP00000516604.1		A0A9L9PXF1

Frequencies

GnomAD3 genomes

AF:

0.0386

AC:

5867

AN:

152018

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00998

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0628

Gnomad OTH

AF:

0.0522

GnomAD3 exomes

AF:

0.0385

AC:

9671

AN:

251450

Hom.:

255

AF XY:

0.0390

AC XY:

5294

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00910

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0337

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0138

Gnomad FIN exome

AF:

0.0389

Gnomad NFE exome

AF:

0.0607

Gnomad OTH exome

AF:

0.0399

GnomAD4 exome

AF:

0.0534

AC:

78096

AN:

1461874

Hom.:

2396

Cov.:

AF XY:

0.0520

AC XY:

37845

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00792

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0394

Gnomad4 NFE exome

AF:

0.0627

Gnomad4 OTH exome

AF:

0.0444

GnomAD4 genome

AF:

0.0385

AC:

5863

AN:

152136

Hom.:

183

Cov.:

AF XY:

0.0358

AC XY:

2666

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00995

Gnomad4 AMR

AF:

0.0264

Gnomad4 ASJ

AF:

0.0326

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0367

Gnomad4 NFE

AF:

0.0627

Gnomad4 OTH

AF:

0.0517

Alfa

AF:

0.0521

Hom.:

341

Bravo

AF:

0.0363

TwinsUK

AF:

0.0666

AC:

247

ALSPAC

AF:

0.0599

AC:

231

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0634

AC:

545

ExAC

AF:

0.0393

AC:

4775

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0568

EpiControl

AF:

0.0618

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MADD-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.53

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

Vest4

0.77

GERP RS

4.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over