Variant 11-47276809-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001376571.1(MADD):c.1041G>A(p.Glu347Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.64 in 1,613,686 control chromosomes in the GnomAD database, including 338,758 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 26060 hom., cov: 31)

Exomes 𝑓: 0.65 ( 312698 hom. )

Consequence

MADD
NM_001376571.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.77

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-47276809-G-A is Benign according to our data. Variant chr11-47276809-G-A is described in ClinVar as [Benign]. Clinvar id is 1243998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 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.1041G>A	p.Glu347Glu	synonymous_variant	5/37	NP_001363500.1
MADD	NM_003682.4 linkuse as main transcript	c.1041G>A	p.Glu347Glu	synonymous_variant	5/36	NP_003673.3	Q8WXG6-1
MADD	NM_001376572.1 linkuse as main transcript	c.1041G>A	p.Glu347Glu	synonymous_variant	5/37	NP_001363501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1 linkuse as main transcript	c.1041G>A	p.Glu347Glu	synonymous_variant	5/37			ENSP00000516604.1		A0A9L9PXF1

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85830

AN:

151888

Hom.:

26041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.684

Gnomad OTH

AF:

0.632

GnomAD3 exomes

AF:

0.593

AC:

149049

AN:

251424

Hom.:

46527

AF XY:

0.603

AC XY:

81930

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.763

Gnomad EAS exome

AF:

0.294

Gnomad SAS exome

AF:

0.537

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.666

GnomAD4 exome

AF:

0.647

AC:

946136

AN:

1461680

Hom.:

312698

Cov.:

AF XY:

0.647

AC XY:

470119

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.562

Gnomad4 ASJ exome

AF:

0.763

Gnomad4 EAS exome

AF:

0.307

Gnomad4 SAS exome

AF:

0.537

Gnomad4 FIN exome

AF:

0.588

Gnomad4 NFE exome

AF:

0.680

Gnomad4 OTH exome

AF:

0.638

GnomAD4 genome

AF:

0.565

AC:

85898

AN:

152006

Hom.:

26060

Cov.:

AF XY:

0.559

AC XY:

41494

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.756

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.684

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.671

Hom.:

73127

Bravo

AF:

0.561

Asia WGS

AF:

0.459

AC:

1600

AN:

3478

EpiCase

AF:

0.707

EpiControl

AF:

0.712

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2019	- -

Deeah syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.2

DANN

Benign

0.80

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over