1-173250332-G-T

Variant names:

• chr1-173250332-G-T
• rs1012507
• ENST00000714430.1:c.-126-10309C>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-10309C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,986 control chromosomes in the GnomAD database, including 8,177 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 0.32 (8177 hom., cov: 33)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-10309C>A		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-43147C>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-43147C>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.-126-10309C>A		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-10309C>A		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-43147C>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49217 AN: 151868 Hom.: 8171 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.324 AC: 49254 AN: 151986 Hom.: 8177 Cov.: 33 AF XY: 0.326 AC XY: 24189 AN XY: 74312

African (AFR) AF: 0.268 AC: 11095 AN: 41462

American (AMR) AF: 0.406 AC: 6204 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 969 AN: 3458

East Asian (EAS) AF: 0.276 AC: 1423 AN: 5160

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4822

European-Finnish (FIN) AF: 0.347 AC: 3654 AN: 10544

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.343 AC: 23335 AN: 67948

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.336 Hom.: 18171

Bravo AF: 0.330

Asia WGS AF: 0.301 AC: 1044 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.63
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs1012507; hg19: chr1-173219471; COSMIC: COSV69336897;