1-173208253-C-G

Variant names:

• chr1-173208253-C-G
• rs1234314
• XM_011509964.3:c.-9G>C

Variant summary

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

The XM_011509964.3(TNFSF4):​c.-9G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,922 control chromosomes in the GnomAD database, including 12,375 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 0.40 (12375 hom., cov: 32)
• Consequence: TNFSF4 XM_011509964.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 50 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-9-1068G>C		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-9-1068G>C		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-1068G>C		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60250 AN: 151802 Hom.: 12355 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.397 AC: 60312 AN: 151922 Hom.: 12375 Cov.: 32 AF XY: 0.401 AC XY: 29787 AN XY: 74222

African (AFR) AF: 0.296 AC: 12258 AN: 41416

American (AMR) AF: 0.518 AC: 7899 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2161 AN: 5144

South Asian (SAS) AF: 0.444 AC: 2136 AN: 4814

European-Finnish (FIN) AF: 0.416 AC: 4387 AN: 10552

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28548 AN: 67950

Other (OTH) AF: 0.417 AC: 880 AN: 2110

Alfa AF: 0.256 Hom.: 610

Bravo AF: 0.399

Asia WGS AF: 0.446 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.39
PhyloP100		-0.72

Splicing

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

Other links and lift over

dbSNP: rs1234314; hg19: chr1-173177392;