rs6425201

Variant names:

• chr1-173043664-C-T
• rs6425201
• NM_005092.4:c.187+275G>A

Variant summary

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

The NM_005092.4(TNFSF18):​c.187+275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,132 control chromosomes in the GnomAD database, including 387 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 0.064 (387 hom., cov: 32)
• Consequence: TNFSF18 NM_005092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 3 publications found

Genes affected

TNFSF18 (HGNC:11932): (TNF superfamily member 18) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptor TNFRSF18/AITR/GITR. It has been shown to modulate T lymphocyte survival in peripheral tissues. This cytokine is also found to be expressed in endothelial cells, and is thought to be important for interaction between T lymphocytes and endothelial cells. [provided by RefSeq, Jul 2008]

ENSG00000224000 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005092.4. 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
	TNFSF18	NM_005092.4	MANE Select	c.187+275G>A		intron	N/A	NP_005083.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF18	ENST00000404377.5	TSL:1 MANE Select	c.187+275G>A		intron	N/A	ENSP00000385470.4
	ENSG00000224000	ENST00000432694.2	TSL:3	n.665+20091C>T		intron	N/A
	ENSG00000224000	ENST00000717048.1		n.324-20209C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9678 AN: 152016 Hom.: 387 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0314

Gnomad SAS AF: 0.0895

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0401

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0637 AC: 9694 AN: 152132 Hom.: 387 Cov.: 32 AF XY: 0.0630 AC XY: 4682 AN XY: 74352

African (AFR) AF: 0.116 AC: 4802 AN: 41496

American (AMR) AF: 0.0661 AC: 1010 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3472

East Asian (EAS) AF: 0.0311 AC: 161 AN: 5180

South Asian (SAS) AF: 0.0886 AC: 427 AN: 4822

European-Finnish (FIN) AF: 0.0181 AC: 192 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0401 AC: 2729 AN: 67990

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0498 Hom.: 396

Bravo AF: 0.0682

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.41
PhyloP100		0.12
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: rs6425201; hg19: chr1-173012804;