rs1234317

Variant names:

• chr1-173218636-C-T
• rs1234317
• ENST00000714430.1:c.-9-11451G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-9-11451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,984 control chromosomes in the GnomAD database, including 4,033 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 0.22 (4033 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• Publications: 12 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	XM_047429896.1	c.148-11451G>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-11451G>A		intron_variant	Intron 2 of 4		XP_047285858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF4	ENST00000714430.1	c.-9-11451G>A		intron_variant	Intron 4 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-9-11451G>A		intron_variant	Intron 4 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-11451G>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32749 AN: 151866 Hom.: 4028 Cov.: 32

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.216 AC: 32759 AN: 151984 Hom.: 4033 Cov.: 32 AF XY: 0.218 AC XY: 16197 AN XY: 74300

African (AFR) AF: 0.0892 AC: 3701 AN: 41476

American (AMR) AF: 0.315 AC: 4803 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1280 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1082 AN: 4806

European-Finnish (FIN) AF: 0.265 AC: 2784 AN: 10516

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17436 AN: 67966

Other (OTH) AF: 0.223 AC: 469 AN: 2106

Alfa AF: 0.244 Hom.: 4452

Bravo AF: 0.216

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		0.84

Splicing

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

Other links and lift over

dbSNP: rs1234317; hg19: chr1-173187775;