1-173407740-T-C

Position:

• chr1-173407740-T-C

Variant summary

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

The XM_047429902.1(TNFSF4):​c.-5286A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 142,644 control chromosomes in the GnomAD database, including 24,018 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 0.57 (24018 hom., cov: 27)
• Consequence: TNFSF4 XM_047429902.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF4	XM_047429902.1	c.-5286A>G		5_prime_UTR_variant	1/5		XP_047285858.1
TNFSF4	XM_047429896.1	c.147+34179A>G		intron_variant			XP_047285852.1
		n.173407740T>C		intergenic_region
LOC100506023	NR_037845.1	n.655+54584A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.574 AC: 81769 AN: 142556 Hom.: 24010 Cov.: 27

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.573 AC: 81794 AN: 142644 Hom.: 24018 Cov.: 27 AF XY: 0.571 AC XY: 39724 AN XY: 69536

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.609

Alfa AF: 0.633 Hom.: 62868

Bravo AF: 0.516

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7526628; hg19: chr1-173376879;