NM_003326.5:c.203-288A>G

Variant names:

• chr1-173187153-T-C
• rs3861950
• NM_003326.5:c.203-288A>G

Variant summary

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

The NM_003326.5(TNFSF4):​c.203-288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,050 control chromosomes in the GnomAD database, including 19,797 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 0.46 (19797 hom., cov: 31)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 29 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	NM_003326.5	MANE Select	c.203-288A>G		intron	N/A	NP_003317.1
	TNFSF4	NM_001297562.2		c.53-288A>G		intron	N/A	NP_001284491.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000281834.4	TSL:1 MANE Select	c.203-288A>G		intron	N/A	ENSP00000281834.3
	TNFSF4	ENST00000367718.5	TSL:1	c.53-288A>G		intron	N/A	ENSP00000356691.1
	TNFSF4	ENST00000714430.1		c.203-288A>G		intron	N/A	ENSP00000519699.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70256 AN: 151934 Hom.: 19733 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.463 AC: 70371 AN: 152050 Hom.: 19797 Cov.: 31 AF XY: 0.460 AC XY: 34211 AN XY: 74328

African (AFR) AF: 0.792 AC: 32868 AN: 41502

American (AMR) AF: 0.428 AC: 6540 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3468

East Asian (EAS) AF: 0.109 AC: 566 AN: 5174

South Asian (SAS) AF: 0.297 AC: 1427 AN: 4806

European-Finnish (FIN) AF: 0.317 AC: 3353 AN: 10578

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22712 AN: 67938

Other (OTH) AF: 0.465 AC: 984 AN: 2114

Alfa AF: 0.382 Hom.: 37968

Bravo AF: 0.486

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.53
PhyloP100		-0.11
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: rs3861950; hg19: chr1-173156292;