rs17350697

Variant names:

• chr1-173364777-C-T
• rs17350697
• ENST00000714430.1:c.-127+59097G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+59097G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,068 control chromosomes in the GnomAD database, including 1,270 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 0.10 (1270 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 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.655+97547G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+59097G>A		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-210-33015G>A		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-10+96416G>A		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15391 AN: 151950 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.101 AC: 15391 AN: 152068 Hom.: 1270 Cov.: 32 AF XY: 0.111 AC XY: 8226 AN XY: 74318

African (AFR) AF: 0.0204 AC: 847 AN: 41510

American (AMR) AF: 0.0645 AC: 986 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5190

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4818

European-Finnish (FIN) AF: 0.304 AC: 3192 AN: 10508

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8472 AN: 67982

Other (OTH) AF: 0.0889 AC: 187 AN: 2104

Alfa AF: 0.105 Hom.: 465

Bravo AF: 0.0754

Asia WGS AF: 0.101 AC: 349 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.55
PhyloP100		0.095

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: rs17350697;

hg19: chr1-173333916;