rs5778749

chr1-173203284-GC-Gchr1-173203284-GC-GCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003326.5(TNFSF4):c.153+3739del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,030 control chromosomes in the GnomAD database, including 1,030 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1030 hom., cov: 31)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF4	NM_003326.5	c.153+3739del		intron_variant		ENST00000281834.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF4	ENST00000281834.4	c.153+3739del		intron_variant		1	NM_003326.5	P1
TNFSF4	ENST00000367718.5	c.3+2026del		intron_variant		1
TNFSF4	ENST00000488053.1	n.414+2026del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16284 AN: 151912 Hom.: 1029 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0709

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.107 AC: 16297 AN: 152030 Hom.: 1030 Cov.: 31 AF XY: 0.109 AC XY: 8093 AN XY: 74330

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0709

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0523

Gnomad4 FIN AF: 0.0690

Gnomad4 NFE AF: 0.0781

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.100 Hom.: 100

Bravo AF: 0.114

Asia WGS AF: 0.0970 AC: 337 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5778749; hg19: chr1-173172423;