chr1-173244796-T-A

Variant names:

• chr1-173244796-T-A
• rs2795288
• ENST00000714430.1:c.-126-4773A>T

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-4773A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,838 control chromosomes in the GnomAD database, including 16,243 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 0.46 (16243 hom., cov: 31)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.518 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.656-4773A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-4773A>T		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-126-4773A>T		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-37611A>T		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69478 AN: 151720 Hom.: 16212 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.458 AC: 69550 AN: 151838 Hom.: 16243 Cov.: 31 AF XY: 0.459 AC XY: 34037 AN XY: 74208

African (AFR) AF: 0.517 AC: 21398 AN: 41404

American (AMR) AF: 0.528 AC: 8053 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3468

East Asian (EAS) AF: 0.442 AC: 2276 AN: 5154

South Asian (SAS) AF: 0.409 AC: 1966 AN: 4804

European-Finnish (FIN) AF: 0.409 AC: 4300 AN: 10524

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28745 AN: 67920

Other (OTH) AF: 0.460 AC: 970 AN: 2110

Alfa AF: 0.441 Hom.: 1835

Bravo AF: 0.473

Asia WGS AF: 0.448 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs2795288; hg19: chr1-173213935;