rs4916314

Variant names:

• chr1-173203019-C-A
• rs4916314
• NM_003326.5:c.153+4005G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-173203019-C-A
• chr1-173203019-C-T

Variant summary

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

The NM_003326.5(TNFSF4):​c.153+4005G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,130 control chromosomes in the GnomAD database, including 2,136 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 0.15 (2136 hom., cov: 32)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

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.153+4005G>T		intron	N/A	NP_003317.1
	TNFSF4	NM_001297562.2		c.3+2292G>T		intron	N/A	NP_001284491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000281834.4	TSL:1 MANE Select	c.153+4005G>T		intron	N/A	ENSP00000281834.3
	TNFSF4	ENST00000367718.5	TSL:1	c.3+2292G>T		intron	N/A	ENSP00000356691.1
	TNFSF4	ENST00000714430.1		c.153+4005G>T		intron	N/A	ENSP00000519699.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22688 AN: 152014 Hom.: 2132 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.149 AC: 22692 AN: 152130 Hom.: 2136 Cov.: 32 AF XY: 0.148 AC XY: 11015 AN XY: 74342

African (AFR) AF: 0.0509 AC: 2111 AN: 41514

American (AMR) AF: 0.158 AC: 2409 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 835 AN: 3472

East Asian (EAS) AF: 0.0233 AC: 121 AN: 5186

South Asian (SAS) AF: 0.171 AC: 822 AN: 4810

European-Finnish (FIN) AF: 0.174 AC: 1841 AN: 10574

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 14002 AN: 67986

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.0803 Hom.: 111

Bravo AF: 0.144

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4916314; hg19: chr1-173172158;