chr1-173343362-T-G

Variant names:

• chr1-173343362-T-G
• rs1539259
• ENST00000714430.1:c.-127+80512A>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+80512A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,116 control chromosomes in the GnomAD database, including 4,365 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 0.23 (4365 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 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.656-103339A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+80512A>C		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-210-11600A>C		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-10+117831A>C		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34338 AN: 151998 Hom.: 4362 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.226 AC: 34337 AN: 152116 Hom.: 4365 Cov.: 32 AF XY: 0.227 AC XY: 16862 AN XY: 74388

African (AFR) AF: 0.134 AC: 5560 AN: 41504

American (AMR) AF: 0.371 AC: 5670 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 730 AN: 3462

East Asian (EAS) AF: 0.450 AC: 2325 AN: 5164

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1971 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16072 AN: 67968

Other (OTH) AF: 0.241 AC: 509 AN: 2108

Alfa AF: 0.235 Hom.: 14891

Bravo AF: 0.238

Asia WGS AF: 0.316 AC: 1100 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	1.3
DANN	Benign	0.47
PhyloP100		-0.52

Splicing

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

Other links and lift over

dbSNP: rs1539259; hg19: chr1-173312501;