dbSNP rs10501320: MADD:c.-88-1579G>C (chr11-47272248-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001376571.1(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
NM_001376571.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.95

Publications

57 publications found

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

MADD-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MADD	NM_001376571.1 link	c.-88-1579G>C		intron_variant	Intron 1 of 36	ENST00000706887.1	NP_001363500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1 link	c.-88-1579G>C		intron_variant	Intron 1 of 36		NM_001376571.1	ENSP00000516604.1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26280

AN:

152028

Hom.:

3065

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.650

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.173

AC:

26277

AN:

152146

Hom.:

3064

Cov.:

AF XY:

0.166

AC XY:

12342

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0437

AC:

1813

AN:

41508

American (AMR)

AF:

0.173

AC:

2649

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

990

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.0822

AC:

397

AN:

4830

European-Finnish (FIN)

AF:

0.176

AC:

1860

AN:

10588

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17905

AN:

67974

Other (OTH)

AF:

0.209

AC:

440

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1043

2087

3130

4174

5217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.93

PhyloP100

6.0

PromoterAI

0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over