1-173429394-T-C

Variant names:

• chr1-173429394-T-C
• rs3934575
• ENST00000367716.3:n.986-10772A>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-227-5420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,244 control chromosomes in the GnomAD database, including 53,936 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 0.84 (53936 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 9 publications found

Genes affected

PRDX6-AS1 (HGNC:54870): (PRDX6 antisense RNA 1)

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

ENSG00000301462 (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 (AFR) allele frequency at 95% confidence interval = 0.916 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.655+32930A>G		intron	N/A
	PRDX6-AS1	NR_125960.1		n.986-10772A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRDX6-AS1	ENST00000367716.3	TSL:1	n.986-10772A>G		intron	N/A
	TNFSF4	ENST00000714430.1		c.-227-5420A>G		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-211+32930A>G		intron	N/A	ENSP00000519727.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127709 AN: 152126 Hom.: 53896 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.839 AC: 127803 AN: 152244 Hom.: 53936 Cov.: 33 AF XY: 0.841 AC XY: 62586 AN XY: 74444

African (AFR) AF: 0.923 AC: 38375 AN: 41560

American (AMR) AF: 0.835 AC: 12763 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3470

East Asian (EAS) AF: 0.686 AC: 3552 AN: 5178

South Asian (SAS) AF: 0.885 AC: 4274 AN: 4828

European-Finnish (FIN) AF: 0.849 AC: 9001 AN: 10600

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54683 AN: 68002

Other (OTH) AF: 0.835 AC: 1767 AN: 2116

Alfa AF: 0.806 Hom.: 4716

Bravo AF: 0.840

Asia WGS AF: 0.809 AC: 2814 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	1.9
DANN	Benign	0.41
PhyloP100		-0.27

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3934575;

hg19: chr1-173398533;