chr1-173257056-T-G

Variant names:

• chr1-173257056-T-G
• rs704840
• ENST00000714430.1:c.-126-17033A>C

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-17033A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,160 control chromosomes in the GnomAD database, including 6,594 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 0.29 (6594 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 31 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
• myocardial infarction, susceptibility to

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

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 = 0.365 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.656-17033A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-17033A>C		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-126-17033A>C		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-49871A>C		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44306 AN: 152042 Hom.: 6581 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.291 AC: 44344 AN: 152160 Hom.: 6594 Cov.: 33 AF XY: 0.293 AC XY: 21767 AN XY: 74386

African (AFR) AF: 0.263 AC: 10930 AN: 41512

American (AMR) AF: 0.373 AC: 5700 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3466

East Asian (EAS) AF: 0.373 AC: 1932 AN: 5178

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3091 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19703 AN: 67992

Other (OTH) AF: 0.285 AC: 602 AN: 2110

Alfa AF: 0.291 Hom.: 28587

Bravo AF: 0.300

Asia WGS AF: 0.313 AC: 1089 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	4.1
DANN	Benign	0.60
PhyloP100		0.090

Splicing

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

Other links and lift over

dbSNP: rs704840; hg19: chr1-173226195;