1-173246233-C-T

Variant names:

• chr1-173246233-C-T
• rs4916315
• ENST00000714430.1:c.-126-6210G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-6210G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,956 control chromosomes in the GnomAD database, including 3,701 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 0.21 (3701 hom., cov: 31)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938
• Publications: 1 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

LOC100506023 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100506023	NR_037845.1		n.656-6210G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-126-6210G>A		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-126-6210G>A		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-39048G>A		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32076 AN: 151838 Hom.: 3695 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.211 AC: 32099 AN: 151956 Hom.: 3701 Cov.: 31 AF XY: 0.213 AC XY: 15803 AN XY: 74276

African (AFR) AF: 0.119 AC: 4941 AN: 41446

American (AMR) AF: 0.317 AC: 4844 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 667 AN: 3464

East Asian (EAS) AF: 0.242 AC: 1255 AN: 5176

South Asian (SAS) AF: 0.201 AC: 970 AN: 4816

European-Finnish (FIN) AF: 0.244 AC: 2570 AN: 10536

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16107 AN: 67938

Other (OTH) AF: 0.214 AC: 451 AN: 2112

Alfa AF: 0.213 Hom.: 471

Bravo AF: 0.217

Asia WGS AF: 0.213 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.89
DANN	Benign	0.25
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs4916315; hg19: chr1-173215372;