1-173275309-C-T

Variant names:

• chr1-173275309-C-T
• rs12403570
• ENST00000714430.1:c.-126-35286G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-35286G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,028 control chromosomes in the GnomAD database, including 3,693 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 0.21 (3693 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-35286G>A		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-68124G>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-68124G>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.-126-35286G>A		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-35286G>A		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-68124G>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32055 AN: 151910 Hom.: 3687 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.211 AC: 32078 AN: 152028 Hom.: 3693 Cov.: 32 AF XY: 0.212 AC XY: 15782 AN XY: 74320

African (AFR) AF: 0.120 AC: 4993 AN: 41500

American (AMR) AF: 0.317 AC: 4826 AN: 15244

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

East Asian (EAS) AF: 0.242 AC: 1245 AN: 5150

South Asian (SAS) AF: 0.199 AC: 958 AN: 4810

European-Finnish (FIN) AF: 0.244 AC: 2580 AN: 10570

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

European-Non Finnish (NFE) AF: 0.236 AC: 16067 AN: 67966

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.210 Hom.: 475

Bravo AF: 0.217

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.18
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs12403570; hg19: chr1-173244448;