1-173186588-C-T

Variant names:

• chr1-173186588-C-T
• NM_003326.5:c.480G>A
• TNFSF4 p.Leu160Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003326.5(TNFSF4):​c.480G>A​(p.Leu160Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L160L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNFSF4 NM_003326.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003326.5. 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
	TNFSF4	NM_003326.5	MANE Select	c.480G>A	p.Leu160Leu	synonymous	Exon 3 of 3	NP_003317.1	P23510-1
	TNFSF4	NM_001297562.2		c.330G>A	p.Leu110Leu	synonymous	Exon 3 of 3	NP_001284491.1	P23510-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000281834.4	TSL:1 MANE Select	c.480G>A	p.Leu160Leu	synonymous	Exon 3 of 3	ENSP00000281834.3	P23510-1
	TNFSF4	ENST00000367718.5	TSL:1	c.330G>A	p.Leu110Leu	synonymous	Exon 3 of 3	ENSP00000356691.1	P23510-2
	TNFSF4	ENST00000714430.1		c.480G>A	p.Leu160Leu	synonymous	Exon 7 of 7	ENSP00000519699.1	P23510-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.064
DANN	Benign	0.39
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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

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

Other links and lift over

hg19: chr1-173155727;