rs2236876

Variant names:

• chr1-173048346-G-A
• rs2236876
• NM_005092.4:c.156+2395C>T

Variant summary

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

The NM_005092.4(TNFSF18):​c.156+2395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,028 control chromosomes in the GnomAD database, including 9,001 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 0.32 (9001 hom., cov: 32)
• Consequence: TNFSF18 NM_005092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.763 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.156+2395C>T		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.156+2395C>T		intron	N/A	ENSP00000385470.4
	ENSG00000224000	ENST00000432694.2	TSL:3	n.666-15527G>A		intron	N/A
	ENSG00000224000	ENST00000717048.1		n.324-15527G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48802 AN: 151912 Hom.: 8992 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.321 AC: 48862 AN: 152028 Hom.: 9001 Cov.: 32 AF XY: 0.326 AC XY: 24245 AN XY: 74336

African (AFR) AF: 0.355 AC: 14685 AN: 41416

American (AMR) AF: 0.387 AC: 5921 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4062 AN: 5184

South Asian (SAS) AF: 0.549 AC: 2648 AN: 4826

European-Finnish (FIN) AF: 0.197 AC: 2089 AN: 10584

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17006 AN: 67950

Other (OTH) AF: 0.346 AC: 731 AN: 2110

Alfa AF: 0.287 Hom.: 12519

Bravo AF: 0.337

Asia WGS AF: 0.630 AC: 2189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.64
PhyloP100		-0.61
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: rs2236876; hg19: chr1-173017486;