ENST00000714430.1:c.-126-22289T>C

Variant names:

• chr1-173262312-A-G
• rs1099447
• ENST00000714430.1:c.-126-22289T>C

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-22289T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,032 control chromosomes in the GnomAD database, including 33,492 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 0.64 (33492 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 4 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

LOC100506023 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.656-22289T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-22289T>C		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-126-22289T>C		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-55127T>C		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97004 AN: 151914 Hom.: 33427 Cov.: 32

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.639 AC: 97126 AN: 152032 Hom.: 33492 Cov.: 32 AF XY: 0.639 AC XY: 47442 AN XY: 74292

African (AFR) AF: 0.914 AC: 37954 AN: 41518

American (AMR) AF: 0.648 AC: 9903 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1801 AN: 3466

East Asian (EAS) AF: 0.443 AC: 2286 AN: 5160

South Asian (SAS) AF: 0.537 AC: 2583 AN: 4812

European-Finnish (FIN) AF: 0.526 AC: 5548 AN: 10544

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35130 AN: 67950

Other (OTH) AF: 0.636 AC: 1343 AN: 2110

Alfa AF: 0.580 Hom.: 3399

Bravo AF: 0.662

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.67
DANN	Benign	0.40
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs1099447; hg19: chr1-173231451;