Variant 11-47328736-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001376571.1(MADD):c.4848+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,942 control chromosomes in the GnomAD database, including 72,370 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 0.34 ( 9765 hom., cov: 33)

Exomes 𝑓: 0.28 ( 62605 hom. )

Consequence

MADD
NM_001376571.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
MADD	NM_001376571.1 linkuse as main transcript	c.4848+32G>A	intron_variant	NP_001363500.1
MADD	NM_003682.4 linkuse as main transcript	c.4839+32G>A	intron_variant	NP_003673.3	Q8WXG6-1
MADD	NM_001376572.1 linkuse as main transcript	c.4836+32G>A	intron_variant	NP_001363501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1 linkuse as main transcript	c.4848+32G>A		intron_variant				ENSP00000516604.1		A0A9L9PXF1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51798

AN:

152052

Hom.:

9760

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.367

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.312

GnomAD3 exomes

AF:

0.339

AC:

84608

AN:

249558

Hom.:

16227

AF XY:

0.330

AC XY:

44540

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.293

Gnomad EAS exome

AF:

0.650

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.279

AC:

408180

AN:

1460772

Hom.:

62605

Cov.:

AF XY:

0.281

AC XY:

203866

AN XY:

726652

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.420

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.637

Gnomad4 SAS exome

AF:

0.363

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.341

AC:

51837

AN:

152170

Hom.:

9765

Cov.:

AF XY:

0.349

AC XY:

25976

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.333

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.632

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.231

Hom.:

954

Bravo

AF:

0.346

Asia WGS

AF:

0.462

AC:

1606

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.9

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over