rs844649

Variant names:

• chr1-173255204-T-C
• rs844649
• ENST00000714430.1:c.-126-15181A>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-15181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,078 control chromosomes in the GnomAD database, including 6,556 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 0.29 (6556 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-15181A>G		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-48019A>G		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-48019A>G		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.-126-15181A>G		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-15181A>G		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-48019A>G		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44189 AN: 151960 Hom.: 6543 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.291 AC: 44226 AN: 152078 Hom.: 6556 Cov.: 32 AF XY: 0.292 AC XY: 21702 AN XY: 74346

African (AFR) AF: 0.264 AC: 10970 AN: 41532

American (AMR) AF: 0.372 AC: 5682 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3468

East Asian (EAS) AF: 0.372 AC: 1921 AN: 5166

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4824

European-Finnish (FIN) AF: 0.291 AC: 3063 AN: 10540

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19603 AN: 67952

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.285 Hom.: 789

Bravo AF: 0.299

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.73
PhyloP100		-0.060

Splicing

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

Other links and lift over

dbSNP: rs844649; hg19: chr1-173224343;