rs4916319

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000714430.1(TNFSF4):​c.-126-57416C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,818 control chromosomes in the GnomAD database, including 19,558 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 0.49 ( 19558 hom., cov: 31)

Consequence

TNFSF4
ENST00000714430.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

Publications

8 publications found
Variant links:
Genes affected
TNFSF4 (HGNC:11934): (TNF superfamily member 4) This gene encodes a cytokine of the tumor necrosis factor (TNF) ligand family. The encoded protein functions in T cell antigen-presenting cell (APC) interactions and mediates adhesion of activated T cells to endothelial cells. Polymorphisms in this gene have been associated with Sjogren's syndrome and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
TNFSF4 Gene-Disease associations (from GenCC):
  • systemic lupus erythematosus
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
LOC100506023
NR_037845.1
n.656-57416C>T
intron
N/A

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TNFSF4
ENST00000714430.1
c.-126-57416C>T
intron
N/AENSP00000519699.1
TNFSF4
ENST00000714470.1
c.-127+34240C>T
intron
N/AENSP00000519727.1
TNFSF4
ENST00000714471.1
c.-9-90254C>T
intron
N/AENSP00000519728.1

Frequencies

GnomAD3 genomes
AF:
0.493
AC:
74730
AN:
151698
Hom.:
19559
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.302
Gnomad AMI
AF:
0.634
Gnomad AMR
AF:
0.511
Gnomad ASJ
AF:
0.597
Gnomad EAS
AF:
0.633
Gnomad SAS
AF:
0.619
Gnomad FIN
AF:
0.535
Gnomad MID
AF:
0.573
Gnomad NFE
AF:
0.570
Gnomad OTH
AF:
0.515
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.492
AC:
74734
AN:
151818
Hom.:
19558
Cov.:
31
AF XY:
0.492
AC XY:
36492
AN XY:
74180
show subpopulations
African (AFR)
AF:
0.302
AC:
12499
AN:
41424
American (AMR)
AF:
0.511
AC:
7779
AN:
15236
Ashkenazi Jewish (ASJ)
AF:
0.597
AC:
2069
AN:
3466
East Asian (EAS)
AF:
0.634
AC:
3253
AN:
5134
South Asian (SAS)
AF:
0.619
AC:
2982
AN:
4820
European-Finnish (FIN)
AF:
0.535
AC:
5646
AN:
10560
Middle Eastern (MID)
AF:
0.585
AC:
172
AN:
294
European-Non Finnish (NFE)
AF:
0.570
AC:
38681
AN:
67872
Other (OTH)
AF:
0.512
AC:
1076
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1873
3747
5620
7494
9367
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
676
1352
2028
2704
3380
<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:
0.542
Hom.:
37750
Bravo
AF:
0.480
Asia WGS
AF:
0.589
AC:
2051
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.3
DANN
Benign
0.66
PhyloP100
-0.096

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs4916319; hg19: chr1-173266578; API