chr1-173251110-T-G

Position:

• chr1-173251110-T-G

Variant summary

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

The XM_047429896.1(TNFSF4):​c.148-43925A>C 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 152,012 control chromosomes in the GnomAD database, including 3,797 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 0.21 (3797 hom., cov: 32)
• Consequence: TNFSF4 XM_047429896.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• 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/exons	MANE	Protein	UniProt
TNFSF4	XM_047429896.1	c.148-43925A>C		intron_variant			XP_047285852.1
TNFSF4	XM_047429902.1	c.19-43925A>C		intron_variant			XP_047285858.1
		n.173251110T>G		intergenic_region
LOC100506023	NR_037845.1	n.656-11087A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32410 AN: 151894 Hom.: 3791 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.213 AC: 32433 AN: 152012 Hom.: 3797 Cov.: 32 AF XY: 0.215 AC XY: 15950 AN XY: 74312

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.215

Alfa AF: 0.143 Hom.: 370

Bravo AF: 0.219

Asia WGS AF: 0.216 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35086785; hg19: chr1-173220249;