1-173208253-C-G

Position:

• chr1-173208253-C-G

Variant summary

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

The XM_011509964.3(TNFSF4):​c.-9G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,922 control chromosomes in the GnomAD database, including 12,375 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 0.40 (12375 hom., cov: 32)
• Consequence: TNFSF4 XM_011509964.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF4	XM_011509964.3	c.-9G>C		5_prime_UTR_variant	1/4		XP_011508266.2
TNFSF4	XM_047429896.1	c.148-1068G>C		intron_variant			XP_047285852.1
TNFSF4	XM_047429902.1	c.19-1068G>C		intron_variant			XP_047285858.1
		n.173208253C>G		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60250 AN: 151802 Hom.: 12355 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.397 AC: 60312 AN: 151922 Hom.: 12375 Cov.: 32 AF XY: 0.401 AC XY: 29787 AN XY: 74222

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.417

Alfa AF: 0.256 Hom.: 610

Bravo AF: 0.399

Asia WGS AF: 0.446 AC: 1546 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	0.41
DANN	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1234314; hg19: chr1-173177392;