1-173209324-C-T

Variant names:

• chr1-173209324-C-T
• rs1234315
• ENST00000714430.1:c.-9-2139G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-9-2139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,002 control chromosomes in the GnomAD database, including 26,309 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 0.57 (26309 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 49 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF4	XM_047429896.1	c.148-2139G>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-2139G>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.-9-2139G>A		intron_variant	Intron 4 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-9-2139G>A		intron_variant	Intron 4 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-2139G>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86323 AN: 151884 Hom.: 26252 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.569 AC: 86437 AN: 152002 Hom.: 26309 Cov.: 32 AF XY: 0.567 AC XY: 42110 AN XY: 74274

African (AFR) AF: 0.796 AC: 33019 AN: 41486

American (AMR) AF: 0.606 AC: 9266 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3466

East Asian (EAS) AF: 0.419 AC: 2164 AN: 5162

South Asian (SAS) AF: 0.461 AC: 2220 AN: 4814

European-Finnish (FIN) AF: 0.438 AC: 4610 AN: 10526

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31761 AN: 67956

Other (OTH) AF: 0.556 AC: 1176 AN: 2114

Alfa AF: 0.503 Hom.: 33796

Bravo AF: 0.591

Asia WGS AF: 0.481 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0030
DANN	Benign	0.35
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs1234315; hg19: chr1-173178463;