rs10912564

Variant names:

• chr1-173201479-C-T
• rs10912564
• NM_003326.5:c.153+5545G>A

Variant summary

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

The NM_003326.5(TNFSF4):​c.153+5545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,922 control chromosomes in the GnomAD database, including 15,356 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 0.42 (15356 hom., cov: 32)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 21 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	NM_003326.5	c.153+5545G>A		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.153+5545G>A		intron_variant	Intron 1 of 2	1	NM_003326.5	ENSP00000281834.3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63442 AN: 151804 Hom.: 15328 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.418 AC: 63507 AN: 151922 Hom.: 15356 Cov.: 32 AF XY: 0.416 AC XY: 30902 AN XY: 74242

African (AFR) AF: 0.669 AC: 27728 AN: 41450

American (AMR) AF: 0.381 AC: 5815 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1402 AN: 3466

East Asian (EAS) AF: 0.0957 AC: 496 AN: 5182

South Asian (SAS) AF: 0.264 AC: 1270 AN: 4808

European-Finnish (FIN) AF: 0.318 AC: 3345 AN: 10516

Middle Eastern (MID) AF: 0.469 AC: 137 AN: 292

European-Non Finnish (NFE) AF: 0.328 AC: 22293 AN: 67936

Other (OTH) AF: 0.414 AC: 871 AN: 2104

Alfa AF: 0.354 Hom.: 8543

Bravo AF: 0.435

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.25
PhyloP100		-1.0
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: rs10912564; hg19: chr1-173170618;