ENST00000714430.1:c.-126-29574C>A

Variant names:

• chr1-173269597-G-T
• rs2022449
• ENST00000714430.1:c.-126-29574C>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-29574C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,028 control chromosomes in the GnomAD database, including 4,380 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 0.24 (4380 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-29574C>A		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-62412C>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-62412C>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.-126-29574C>A		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-29574C>A		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-62412C>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36080 AN: 151910 Hom.: 4374 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.237 AC: 36104 AN: 152028 Hom.: 4380 Cov.: 32 AF XY: 0.238 AC XY: 17681 AN XY: 74308

African (AFR) AF: 0.212 AC: 8802 AN: 41478

American (AMR) AF: 0.326 AC: 4969 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1253 AN: 5160

South Asian (SAS) AF: 0.200 AC: 967 AN: 4828

European-Finnish (FIN) AF: 0.243 AC: 2569 AN: 10576

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

European-Non Finnish (NFE) AF: 0.237 AC: 16103 AN: 67962

Other (OTH) AF: 0.230 AC: 484 AN: 2102

Alfa AF: 0.235 Hom.: 765

Bravo AF: 0.248

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.79
DANN	Benign	0.21
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs2022449; hg19: chr1-173238736;