rs6661173

Variant names:

• chr1-173191144-G-A
• rs6661173
• NM_003326.5:c.154-2575C>T

Variant summary

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

The NM_003326.5(TNFSF4):​c.154-2575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,138 control chromosomes in the GnomAD database, including 996 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 0.11 (996 hom., cov: 32)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	NM_003326.5	c.154-2575C>T		intron_variant	Intron 1 of 2	ENST00000281834.4	NP_003317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000281834.4	c.154-2575C>T		intron_variant	Intron 1 of 2	1	NM_003326.5	ENSP00000281834.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15998 AN: 152020 Hom.: 993 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.0572

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0974

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

GnomAD4 genome AF: 0.105 AC: 16017 AN: 152138 Hom.: 996 Cov.: 32 AF XY: 0.107 AC XY: 7927 AN XY: 74372

African (AFR) AF: 0.155 AC: 6419 AN: 41492

American (AMR) AF: 0.162 AC: 2473 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 246 AN: 3472

East Asian (EAS) AF: 0.0759 AC: 392 AN: 5168

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4824

European-Finnish (FIN) AF: 0.0596 AC: 631 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0782 AC: 5320 AN: 68012

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.108 Hom.: 147

Bravo AF: 0.114

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.70
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6661173; hg19: chr1-173160283;