Menu
GeneBe

11-70203468-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003824.4(FADD):c.9G>T(p.Pro3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000785 in 1,581,698 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P3P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00079 ( 7 hom. )

Consequence

FADD
NM_003824.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.31
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-70203468-G-T is Benign according to our data. Variant chr11-70203468-G-T is described in ClinVar as [Benign]. Clinvar id is 713705.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.31 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FADDNM_003824.4 linkuse as main transcriptc.9G>T p.Pro3= synonymous_variant 1/2 ENST00000301838.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FADDENST00000301838.5 linkuse as main transcriptc.9G>T p.Pro3= synonymous_variant 1/21 NM_003824.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000724
AC:
110
AN:
151910
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00125
Gnomad FIN
AF:
0.00481
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000677
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00155
AC:
297
AN:
191334
Hom.:
3
AF XY:
0.00151
AC XY:
158
AN XY:
104708
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000689
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00173
Gnomad FIN exome
AF:
0.00678
Gnomad NFE exome
AF:
0.00158
Gnomad OTH exome
AF:
0.000993
GnomAD4 exome
AF:
0.000792
AC:
1132
AN:
1429672
Hom.:
7
Cov.:
34
AF XY:
0.000809
AC XY:
573
AN XY:
708616
show subpopulations
Gnomad4 AFR exome
AF:
0.0000917
Gnomad4 AMR exome
AF:
0.0000250
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00181
Gnomad4 FIN exome
AF:
0.00549
Gnomad4 NFE exome
AF:
0.000572
Gnomad4 OTH exome
AF:
0.00130
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000724
AC:
110
AN:
152026
Hom.:
0
Cov.:
33
AF XY:
0.000861
AC XY:
64
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000145
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00125
Gnomad4 FIN
AF:
0.00481
Gnomad4 NFE
AF:
0.000677
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000597
Hom.:
0
Bravo
AF:
0.000332
Asia WGS
AF:
0.000289
AC:
1
AN:
3474

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

FADD-related immunodeficiency Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 03, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
7.5
Dann
Benign
0.92

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.

Other links and lift over

dbSNP: rs201376917; hg19: chr11-70049574; API