rs10798269

Positions:

• chr1-173340574-A-G
• chr1-173340574-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047429896.1(TNFSF4):​c.147+101345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,846 control chromosomes in the GnomAD database, including 30,562 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 0.63 (30562 hom., cov: 30)
• Consequence: TNFSF4 XM_047429896.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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]

LOC100506023 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF4	XM_047429896.1	c.147+101345T>C		intron_variant			XP_047285852.1
TNFSF4	XM_047429902.1	c.18+61685T>C		intron_variant			XP_047285858.1
LOC100506023	NR_037845.1	n.656-100551T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96002 AN: 151728 Hom.: 30558 Cov.: 30

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.632 AC: 96033 AN: 151846 Hom.: 30562 Cov.: 30 AF XY: 0.636 AC XY: 47168 AN XY: 74166

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.658

Alfa AF: 0.644 Hom.: 70527

Bravo AF: 0.627

Asia WGS AF: 0.616 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10798269; hg19: chr1-173309713;