rs1234313

Positions:

• chr1-173197108-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003326.5(TNFSF4):​c.154-8539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,156 control chromosomes in the GnomAD database, including 39,940 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 0.71 (39940 hom., cov: 33)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF4	NM_003326.5	c.154-8539T>C		intron_variant		ENST00000281834.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF4	ENST00000281834.4	c.154-8539T>C		intron_variant		1	NM_003326.5	P1
TNFSF4	ENST00000367718.5	c.3+8203T>C		intron_variant		1
TNFSF4	ENST00000488053.1	n.414+8203T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108604 AN: 152038 Hom.: 39886 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.714 AC: 108711 AN: 152156 Hom.: 39940 Cov.: 33 AF XY: 0.710 AC XY: 52839 AN XY: 74382

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.742

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.720

Alfa AF: 0.687 Hom.: 47668

Bravo AF: 0.718

Asia WGS AF: 0.497 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1234313; hg19: chr1-173166247;