rs10489266

Variant names:

• chr1-173209314-A-G
• rs10489266
• ENST00000714430.1:c.-9-2129T>C

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-9-2129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0776 in 152,236 control chromosomes in the GnomAD database, including 535 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 0.078 (535 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	XM_047429896.1	c.148-2129T>C		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-2129T>C		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.-9-2129T>C		intron_variant	Intron 4 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-9-2129T>C		intron_variant	Intron 4 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-2129T>C		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11802 AN: 152118 Hom.: 536 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0945

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.0776 AC: 11806 AN: 152236 Hom.: 535 Cov.: 32 AF XY: 0.0780 AC XY: 5805 AN XY: 74434

African (AFR) AF: 0.0468 AC: 1944 AN: 41552

American (AMR) AF: 0.0777 AC: 1188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3468

East Asian (EAS) AF: 0.0239 AC: 124 AN: 5184

South Asian (SAS) AF: 0.116 AC: 561 AN: 4824

European-Finnish (FIN) AF: 0.0890 AC: 944 AN: 10604

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0945 AC: 6424 AN: 67990

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.0894 Hom.: 1982

Bravo AF: 0.0749

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.87
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs10489266; hg19: chr1-173178453;