Variant rs326217 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001376571.1(MADD):c.1440T>C(p.Asn480Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,609,658 control chromosomes in the GnomAD database, including 71,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6496 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65389 hom. )

Consequence

MADD
NM_001376571.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0140

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-47281724-T-C is Benign according to our data. Variant chr11-47281724-T-C is described in ClinVar as [Benign]. Clinvar id is 1321156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.014 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.365 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.1440T>C	p.Asn480Asn	synonymous_variant	8/37	NP_001363500.1
MADD	NM_003682.4 linkuse as main transcript	c.1440T>C	p.Asn480Asn	synonymous_variant	8/36	NP_003673.3	Q8WXG6-1
MADD	NM_001376572.1 linkuse as main transcript	c.1440T>C	p.Asn480Asn	synonymous_variant	8/37	NP_001363501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MADD	ENST00000706887.1 linkuse as main transcript	c.1440T>C	p.Asn480Asn	synonymous_variant	8/37			ENSP00000516604.1		A0A9L9PXF1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44159

AN:

151906

Hom.:

6476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.321

GnomAD3 exomes

AF:

0.303

AC:

75931

AN:

250342

Hom.:

11848

AF XY:

0.302

AC XY:

40896

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.277

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.297

AC:

433406

AN:

1457634

Hom.:

65389

Cov.:

AF XY:

0.297

AC XY:

215449

AN XY:

724876

show subpopulations

Gnomad4 AFR exome

AF:

0.252

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.376

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.296

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.291

AC:

44224

AN:

152024

Hom.:

6496

Cov.:

AF XY:

0.290

AC XY:

21569

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.373

Gnomad4 ASJ

AF:

0.374

Gnomad4 EAS

AF:

0.286

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.307

Hom.:

17254

Bravo

AF:

0.300

Asia WGS

AF:

0.322

AC:

1121

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deeah syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.56

CADD

Benign

3.2

DANN

Benign

0.39

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