1-173315060-G-T

Variant names:

• chr1-173315060-G-T
• rs4916321
• ENST00000714430.1:c.-126-75037C>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-75037C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0493 in 152,212 control chromosomes in the GnomAD database, including 268 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 0.049 (268 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 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.656-75037C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-75037C>A		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-127+16619C>A		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-107875C>A		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7499 AN: 152094 Hom.: 266 Cov.: 33

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0828

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0554

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

GnomAD4 genome AF: 0.0493 AC: 7510 AN: 152212 Hom.: 268 Cov.: 33 AF XY: 0.0495 AC XY: 3685 AN XY: 74418

African (AFR) AF: 0.0121 AC: 502 AN: 41546

American (AMR) AF: 0.0834 AC: 1273 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3470

East Asian (EAS) AF: 0.108 AC: 559 AN: 5172

South Asian (SAS) AF: 0.0542 AC: 262 AN: 4830

European-Finnish (FIN) AF: 0.0491 AC: 521 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 4010 AN: 68000

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0528 Hom.: 306

Bravo AF: 0.0531

Asia WGS AF: 0.0710 AC: 247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.8
DANN	Benign	0.77
PhyloP100		-0.073

Splicing

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

Other links and lift over

dbSNP: rs4916321; hg19: chr1-173284199;