1-173343567-G-C

Variant names:

• chr1-173343567-G-C
• rs1539256
• ENST00000714430.1:c.-127+80307C>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+80307C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,158 control chromosomes in the GnomAD database, including 871 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 0.099 (871 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 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.656-103544C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+80307C>G		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-210-11805C>G		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-10+117626C>G		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14950 AN: 152040 Hom.: 866 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0986 AC: 14998 AN: 152158 Hom.: 871 Cov.: 32 AF XY: 0.101 AC XY: 7491 AN XY: 74392

African (AFR) AF: 0.101 AC: 4211 AN: 41498

American (AMR) AF: 0.0773 AC: 1182 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3466

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5172

South Asian (SAS) AF: 0.133 AC: 643 AN: 4826

European-Finnish (FIN) AF: 0.120 AC: 1266 AN: 10592

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5927 AN: 67990

Other (OTH) AF: 0.0762 AC: 161 AN: 2114

Alfa AF: 0.0962 Hom.: 78

Bravo AF: 0.0957

Asia WGS AF: 0.221 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs1539256; hg19: chr1-173312706;