rs3861950

chr1-173187153-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003326.5(TNFSF4):c.203-288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,050 control chromosomes in the GnomAD database, including 19,797 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 0.46 (19797 hom., cov: 31)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF4	NM_003326.5	c.203-288A>G		intron_variant		ENST00000281834.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF4	ENST00000281834.4	c.203-288A>G		intron_variant		1	NM_003326.5	P1
TNFSF4	ENST00000367718.5	c.53-288A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70256 AN: 151934 Hom.: 19733 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.463 AC: 70371 AN: 152050 Hom.: 19797 Cov.: 31 AF XY: 0.460 AC XY: 34211 AN XY: 74328

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.465

Alfa AF: 0.363 Hom.: 14303

Bravo AF: 0.486

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.6
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3861950; hg19: chr1-173156292;