1-173407740-T-C

Variant names:

• chr1-173407740-T-C
• rs7526628
• XM_047429902.1:c.-5286A>G

Variant summary

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

The XM_047429902.1(TNFSF4):​c.-5286A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 142,644 control chromosomes in the GnomAD database, including 24,018 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 0.57 (24018 hom., cov: 27)
• Consequence: TNFSF4 XM_047429902.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 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+54584A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+16134A>G		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-211+54584A>G		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-10+53453A>G		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 81769 AN: 142556 Hom.: 24010 Cov.: 27

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.573 AC: 81794 AN: 142644 Hom.: 24018 Cov.: 27 AF XY: 0.571 AC XY: 39724 AN XY: 69536

African (AFR) AF: 0.387 AC: 14501 AN: 37484

American (AMR) AF: 0.519 AC: 7511 AN: 14484

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2530 AN: 3398

East Asian (EAS) AF: 0.266 AC: 1069 AN: 4020

South Asian (SAS) AF: 0.650 AC: 2950 AN: 4538

European-Finnish (FIN) AF: 0.694 AC: 6842 AN: 9854

Middle Eastern (MID) AF: 0.739 AC: 210 AN: 284

European-Non Finnish (NFE) AF: 0.675 AC: 44379 AN: 65710

Other (OTH) AF: 0.609 AC: 1208 AN: 1982

Alfa AF: 0.612 Hom.: 91428

Bravo AF: 0.516

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.80
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs7526628; hg19: chr1-173376879;