chr1-173340574-A-G

Variant names:

• chr1-173340574-A-G
• rs10798269
• ENST00000714430.1:c.-127+83300T>C

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+83300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,846 control chromosomes in the GnomAD database, including 30,562 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 0.63 (30562 hom., cov: 30)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 41 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

LOC100506023 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714430.1. 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
	LOC100506023	NR_037845.1		n.656-100551T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+83300T>C		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-210-8812T>C		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-10+120619T>C		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96002 AN: 151728 Hom.: 30558 Cov.: 30

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.632 AC: 96033 AN: 151846 Hom.: 30562 Cov.: 30 AF XY: 0.636 AC XY: 47168 AN XY: 74166

African (AFR) AF: 0.552 AC: 22854 AN: 41382

American (AMR) AF: 0.688 AC: 10493 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3324 AN: 5144

South Asian (SAS) AF: 0.682 AC: 3281 AN: 4808

European-Finnish (FIN) AF: 0.714 AC: 7529 AN: 10548

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44137 AN: 67914

Other (OTH) AF: 0.658 AC: 1390 AN: 2114

Alfa AF: 0.641 Hom.: 106321

Bravo AF: 0.627

Asia WGS AF: 0.616 AC: 2141 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	1.3
DANN	Benign	0.78
PhyloP100		-0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10798269; hg19: chr1-173309713;