chr1-173332958-A-G

Variant names:

• chr1-173332958-A-G
• rs947505
• ENST00000714430.1:c.-127+90916T>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+90916T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,294 control chromosomes in the GnomAD database, including 50,535 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 0.81 (50535 hom., cov: 34)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 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.656-92935T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+90916T>C		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-210-1196T>C		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-125773T>C		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123499 AN: 152176 Hom.: 50507 Cov.: 34

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.811 AC: 123577 AN: 152294 Hom.: 50535 Cov.: 34 AF XY: 0.811 AC XY: 60414 AN XY: 74474

African (AFR) AF: 0.695 AC: 28865 AN: 41536

American (AMR) AF: 0.859 AC: 13139 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3052 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4140 AN: 5188

South Asian (SAS) AF: 0.843 AC: 4074 AN: 4832

European-Finnish (FIN) AF: 0.851 AC: 9028 AN: 10610

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58462 AN: 68032

Other (OTH) AF: 0.834 AC: 1764 AN: 2116

Alfa AF: 0.846 Hom.: 85341

Bravo AF: 0.806

Asia WGS AF: 0.799 AC: 2776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		0.0050

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs947505;

hg19: chr1-173302097;