Variant 11-70203417-A-G 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_003824.4(FADD):c.-43A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 1,548,628 control chromosomes in the GnomAD database, including 249,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24505 hom., cov: 32)

Exomes 𝑓: 0.57 ( 224738 hom. )

Consequence

FADD
NM_003824.4 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.149

Variant links:

Genes affected

FADD (HGNC:3573): (Fas associated via death domain) The protein encoded by this gene is an adaptor molecule that interacts with various cell surface receptors and mediates cell apoptotic signals. Through its C-terminal death domain, this protein can be recruited by TNFRSF6/Fas-receptor, tumor necrosis factor receptor, TNFRSF25, and TNFSF10/TRAIL-receptor, and thus it participates in the death signaling initiated by these receptors. Interaction of this protein with the receptors unmasks the N-terminal effector domain of this protein, which allows it to recruit caspase-8, and thereby activate the cysteine protease cascade. Knockout studies in mice also suggest the importance of this protein in early T cell development. [provided by RefSeq, Jul 2008]

FADD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 11-70203417-A-G is Benign according to our data. Variant chr11-70203417-A-G is described in ClinVar as [Benign]. Clinvar id is 1174392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FADD	NM_003824.4 linkuse as main transcript	c.-43A>G		5_prime_UTR_variant	1/2	ENST00000301838.5	NP_003815.1	Q13158

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FADD	ENST00000301838 linkuse as main transcript	c.-43A>G		5_prime_UTR_variant	1/2	1	NM_003824.4	ENSP00000301838.5		Q13158

Frequencies

GnomAD3 genomes

AF:

0.565

AC:

85824

AN:

151840

Hom.:

24473

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.634

Gnomad EAS

AF:

0.648

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.561

GnomAD3 exomes

AF:

0.534

AC:

79246

AN:

148398

Hom.:

21703

AF XY:

0.531

AC XY:

42644

AN XY:

80332

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.450

Gnomad ASJ exome

AF:

0.614

Gnomad EAS exome

AF:

0.616

Gnomad SAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.570

Gnomad OTH exome

AF:

0.561

GnomAD4 exome

AF:

0.565

AC:

789684

AN:

1396672

Hom.:

224738

Cov.:

AF XY:

0.562

AC XY:

387003

AN XY:

689120

show subpopulations

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.623

Gnomad4 EAS exome

AF:

0.632

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.560

Gnomad4 NFE exome

AF:

0.575

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.565

AC:

85907

AN:

151956

Hom.:

24505

Cov.:

AF XY:

0.562

AC XY:

41745

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.588

Gnomad4 AMR

AF:

0.481

Gnomad4 ASJ

AF:

0.634

Gnomad4 EAS

AF:

0.648

Gnomad4 SAS

AF:

0.438

Gnomad4 FIN

AF:

0.561

Gnomad4 NFE

AF:

0.573

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.575

Hom.:

4629

Bravo

AF:

0.561

Asia WGS

AF:

0.548

AC:

1905

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.4

DANN

Benign

0.53

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over