rs6697570

Variant names:

• chr1-173284964-T-C
• rs6697570
• ENST00000714430.1:c.-126-44941A>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-44941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,114 control chromosomes in the GnomAD database, including 7,589 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 0.30 (7589 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• 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
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.389 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.656-44941A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-44941A>G		intron	N/A	ENSP00000519699.1	P23510-1
	TNFSF4	ENST00000714470.1		c.-126-44941A>G		intron	N/A	ENSP00000519727.1	P23510-1
	TNFSF4	ENST00000714471.1		c.-9-77779A>G		intron	N/A	ENSP00000519728.1	P23510-1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46016 AN: 151996 Hom.: 7583 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.303 AC: 46049 AN: 152114 Hom.: 7589 Cov.: 32 AF XY: 0.306 AC XY: 22737 AN XY: 74360

African (AFR) AF: 0.176 AC: 7319 AN: 41530

American (AMR) AF: 0.398 AC: 6069 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5168

South Asian (SAS) AF: 0.309 AC: 1490 AN: 4822

European-Finnish (FIN) AF: 0.371 AC: 3926 AN: 10574

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23813 AN: 67976

Other (OTH) AF: 0.312 AC: 659 AN: 2112

Alfa AF: 0.319 Hom.: 1016

Bravo AF: 0.303

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.76
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs6697570; hg19: chr1-173254103;