1-173280199-C-T

Variant names:

• chr1-173280199-C-T
• rs67638449
• ENST00000714430.1:c.-126-40176G>A

Variant summary

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

The ENST00000714430.1(TNFSF4):​c.-126-40176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,028 control chromosomes in the GnomAD database, including 3,781 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 0.21 (3781 hom., cov: 32)
• Consequence: TNFSF4 ENST00000714430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100506023	NR_037845.1	n.656-40176G>A		intron_variant	Intron 2 of 2
TNFSF4	XM_047429896.1	c.148-73014G>A		intron_variant	Intron 2 of 4		XP_047285852.1
TNFSF4	XM_047429902.1	c.19-73014G>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.-126-40176G>A		intron_variant	Intron 3 of 6			ENSP00000519699.1
TNFSF4	ENST00000714470.1	c.-126-40176G>A		intron_variant	Intron 3 of 6			ENSP00000519727.1
TNFSF4	ENST00000714471.1	c.-9-73014G>A		intron_variant	Intron 3 of 5			ENSP00000519728.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32364 AN: 151910 Hom.: 3775 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.213 AC: 32388 AN: 152028 Hom.: 3781 Cov.: 32 AF XY: 0.214 AC XY: 15925 AN XY: 74308

African (AFR) AF: 0.121 AC: 5031 AN: 41512

American (AMR) AF: 0.319 AC: 4857 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3470

East Asian (EAS) AF: 0.241 AC: 1236 AN: 5132

South Asian (SAS) AF: 0.200 AC: 964 AN: 4820

European-Finnish (FIN) AF: 0.246 AC: 2598 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16266 AN: 67958

Other (OTH) AF: 0.216 AC: 456 AN: 2112

Alfa AF: 0.215 Hom.: 479

Bravo AF: 0.219

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs67638449; hg19: chr1-173249338;