1-173364690-G-T

Variant names:

• chr1-173364690-G-T
• rs4916334
• ENST00000714430.1:c.-127+59184C>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+59184C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,562 control chromosomes in the GnomAD database, including 36,803 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 0.70 (36803 hom., cov: 31)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• 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

LOC100506023 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 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.655+97634C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+59184C>A		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-210-32928C>A		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-10+96503C>A		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105274 AN: 151446 Hom.: 36783 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.695 AC: 105339 AN: 151562 Hom.: 36803 Cov.: 31 AF XY: 0.695 AC XY: 51499 AN XY: 74052

African (AFR) AF: 0.774 AC: 31993 AN: 41356

American (AMR) AF: 0.713 AC: 10855 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2250 AN: 3472

East Asian (EAS) AF: 0.645 AC: 3329 AN: 5160

South Asian (SAS) AF: 0.684 AC: 3286 AN: 4804

European-Finnish (FIN) AF: 0.692 AC: 7209 AN: 10424

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44101 AN: 67828

Other (OTH) AF: 0.704 AC: 1479 AN: 2100

Alfa AF: 0.660 Hom.: 134773

Bravo AF: 0.700

Asia WGS AF: 0.628 AC: 2179 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.88
DANN	Benign	0.49
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs4916334; hg19: chr1-173333829;