rs6701066

Variant names:

• chr1-173383558-G-C
• rs6701066
• ENST00000714430.1:c.-127+40316C>G

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-127+40316C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,106 control chromosomes in the GnomAD database, including 10,020 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 0.34 (10020 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000714430.1. 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
	LOC100506023	NR_037845.1		n.655+78766C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF4	ENST00000714430.1		c.-127+40316C>G		intron	N/A	ENSP00000519699.1
	TNFSF4	ENST00000714470.1		c.-210-51796C>G		intron	N/A	ENSP00000519727.1
	TNFSF4	ENST00000714471.1		c.-10+77635C>G		intron	N/A	ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52403 AN: 151986 Hom.: 10019 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.345 AC: 52412 AN: 152106 Hom.: 10020 Cov.: 32 AF XY: 0.348 AC XY: 25896 AN XY: 74362

African (AFR) AF: 0.190 AC: 7897 AN: 41514

American (AMR) AF: 0.302 AC: 4613 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1008 AN: 5180

South Asian (SAS) AF: 0.433 AC: 2091 AN: 4824

European-Finnish (FIN) AF: 0.510 AC: 5381 AN: 10556

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28620 AN: 67958

Other (OTH) AF: 0.375 AC: 793 AN: 2112

Alfa AF: 0.376 Hom.: 1589

Bravo AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		0.65

Splicing

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

Other links and lift over

dbSNP: rs6701066; hg19: chr1-173352697;