1-173208097-C-T

Variant names:

• chr1-173208097-C-T
• rs45454293
• XM_011509964.3:c.148G>A

Variant summary

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

The XM_011509964.3(TNFSF4):​c.148G>A​(p.Asp50Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,146 control chromosomes in the GnomAD database, including 460 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.070 (460 hom., cov: 32)
• Consequence: TNFSF4 XM_011509964.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 20 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	XM_011509964.3	c.148G>A	p.Asp50Asn	missense_variant	Exon 1 of 4		XP_011508266.2
TNFSF4	XM_047429896.1	c.148-912G>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-912G>A		intron_variant	Intron 2 of 4		XP_047285858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000714430.1	c.-9-912G>A		intron_variant	Intron 4 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-9-912G>A		intron_variant	Intron 4 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-912G>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10604 AN: 152028 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0694

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

GnomAD4 genome AF: 0.0697 AC: 10607 AN: 152146 Hom.: 460 Cov.: 32 AF XY: 0.0709 AC XY: 5274 AN XY: 74366

African (AFR) AF: 0.0250 AC: 1037 AN: 41516

American (AMR) AF: 0.110 AC: 1679 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.147 AC: 762 AN: 5174

South Asian (SAS) AF: 0.0915 AC: 441 AN: 4822

European-Finnish (FIN) AF: 0.0648 AC: 684 AN: 10558

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5551 AN: 67996

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0644 Hom.: 140

Bravo AF: 0.0689

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.2
DANN	Benign	0.59
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs45454293; hg19: chr1-173177236;