chr1-173208826-C-A

Variant names:

• chr1-173208826-C-A
• rs12027059
• XM_011509964.3:c.-582G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The XM_011509964.3(TNFSF4):​c.-582G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.000063 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: TNFSF4 XM_011509964.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-9-1641G>T		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-9-1641G>T		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-9-1641G>T		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0000629 AC: 8 AN: 127086 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000889

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000152

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000167

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000629 AC: 8 AN: 127152 Hom.: 0 Cov.: 31 AF XY: 0.0000988 AC XY: 6 AN XY: 60740

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000886 AC: 3 AN: 33858

American (AMR) AF: 0.000242 AC: 3 AN: 12394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3194

East Asian (EAS) AF: 0.00 AC: 0 AN: 4392

South Asian (SAS) AF: 0.00 AC: 0 AN: 4034

European-Finnish (FIN) AF: 0.000152 AC: 1 AN: 6590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 232

European-Non Finnish (NFE) AF: 0.0000167 AC: 1 AN: 59882

Other (OTH) AF: 0.00 AC: 0 AN: 1786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000169 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.45
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs12027059; hg19: chr1-173177965;