rs10798265

Variant names:

• chr1-173196320-C-T
• rs10798265
• NM_003326.5:c.154-7751G>A

Variant summary

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

The NM_003326.5(TNFSF4):​c.154-7751G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,128 control chromosomes in the GnomAD database, including 2,623 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 0.13 (2623 hom., cov: 32)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	NM_003326.5	c.154-7751G>A		intron_variant	Intron 1 of 2	ENST00000281834.4	NP_003317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000281834.4	c.154-7751G>A		intron_variant	Intron 1 of 2	1	NM_003326.5	ENSP00000281834.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19955 AN: 152010 Hom.: 2621 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0722

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0835

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.131 AC: 19980 AN: 152128 Hom.: 2623 Cov.: 32 AF XY: 0.130 AC XY: 9685 AN XY: 74344

African (AFR) AF: 0.344 AC: 14270 AN: 41476

American (AMR) AF: 0.0720 AC: 1101 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3464

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0411 AC: 198 AN: 4816

European-Finnish (FIN) AF: 0.0835 AC: 885 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0434 AC: 2952 AN: 67996

Other (OTH) AF: 0.119 AC: 251 AN: 2116

Alfa AF: 0.103 Hom.: 244

Bravo AF: 0.142

Asia WGS AF: 0.0390 AC: 140 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	1.9
DANN	Benign	0.65
PhyloP100		-0.22
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: rs10798265; hg19: chr1-173165459;