1-173192561-G-T

Variant names:

• chr1-173192561-G-T
• rs10912558
• NM_003326.5:c.154-3992C>A

Variant summary

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

The NM_003326.5(TNFSF4):​c.154-3992C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,122 control chromosomes in the GnomAD database, including 2,742 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 0.18 (2742 hom., cov: 32)
• Consequence: TNFSF4 NM_003326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003326.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	NM_003326.5	MANE Select	c.154-3992C>A		intron	N/A	NP_003317.1
	TNFSF4	NM_001297562.2		c.4-3992C>A		intron	N/A	NP_001284491.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000281834.4	TSL:1 MANE Select	c.154-3992C>A		intron	N/A	ENSP00000281834.3
	TNFSF4	ENST00000367718.5	TSL:1	c.4-3992C>A		intron	N/A	ENSP00000356691.1
	TNFSF4	ENST00000714430.1		c.154-3992C>A		intron	N/A	ENSP00000519699.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28004 AN: 152004 Hom.: 2737 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.184 AC: 28026 AN: 152122 Hom.: 2742 Cov.: 32 AF XY: 0.182 AC XY: 13557 AN XY: 74348

African (AFR) AF: 0.171 AC: 7106 AN: 41514

American (AMR) AF: 0.170 AC: 2593 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3464

East Asian (EAS) AF: 0.0235 AC: 122 AN: 5188

South Asian (SAS) AF: 0.173 AC: 832 AN: 4820

European-Finnish (FIN) AF: 0.173 AC: 1828 AN: 10572

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14028 AN: 67982

Other (OTH) AF: 0.202 AC: 425 AN: 2106

Alfa AF: 0.186 Hom.: 4002

Bravo AF: 0.184

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.26
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10912558; hg19: chr1-173161700;