TNFSF4 p.Asp50Asn

Variant names:

• chr1-173208097-C-T
• rs45454293
• XM_011509964.3:c.148G>A
• TNFSF4 p.Asp50Asn

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000899982.1(TNFSF4):​c.-141G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,146 control chromosomes in the GnomAD database, including 460 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 0.070 (460 hom., cov: 32)
• Consequence: TNFSF4 ENST00000899982.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 20 publications found

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
• myocardial infarction, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

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 = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000899982.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000899982.1		c.-141G>A		5_prime_UTR	Exon 2 of 5	ENSP00000570041.1
	TNFSF4	ENST00000714430.1		c.-9-912G>A		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-9-912G>A		intron	N/A	ENSP00000519727.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10604 AN: 152028 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0694

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0697 AC: 10607 AN: 152146 Hom.: 460 Cov.: 32 AF XY: 0.0709 AC XY: 5274 AN XY: 74366

African (AFR) AF: 0.0250 AC: 1037 AN: 41516

American (AMR) AF: 0.110 AC: 1679 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.147 AC: 762 AN: 5174

South Asian (SAS) AF: 0.0915 AC: 441 AN: 4822

European-Finnish (FIN) AF: 0.0648 AC: 684 AN: 10558

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5551 AN: 67996

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0644 Hom.: 140

Bravo AF: 0.0689

Asia WGS AF: 0.111 AC: 384 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	7.2
DANN	Benign	0.59
PhyloP100		-0.43

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs45454293;

hg19: chr1-173177236;