ENST00000714430.1:c.-126-39795G>A

Variant names:

• chr1-173279818-C-T
• rs844665
• ENST00000714430.1:c.-126-39795G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-39795G>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 152,134 control chromosomes in the GnomAD database, including 1,701 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 (1701 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 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.656-39795G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-39795G>A		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-126-39795G>A		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-72633G>A		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19929 AN: 152016 Hom.: 1697 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.131 AC: 19963 AN: 152134 Hom.: 1701 Cov.: 32 AF XY: 0.131 AC XY: 9720 AN XY: 74378

African (AFR) AF: 0.239 AC: 9919 AN: 41490

American (AMR) AF: 0.121 AC: 1849 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3472

East Asian (EAS) AF: 0.176 AC: 910 AN: 5168

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4824

European-Finnish (FIN) AF: 0.0637 AC: 676 AN: 10604

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5410 AN: 67996

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.116 Hom.: 230

Bravo AF: 0.139

Asia WGS AF: 0.149 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs844665; hg19: chr1-173248957;