rs756517100

Variant names:

• chr1-1203906-C-A
• rs756517100
• NM_004195.3:c.664G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-1203906-C-A
• chr1-1203906-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004195.3(TNFRSF18):​c.664G>T​(p.Glu222*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNFRSF18 NM_004195.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• Publications: 0 publications found

Genes affected

TNFRSF18 (HGNC:11914): (TNF receptor superfamily member 18) This gene encodes a member of the TNF-receptor superfamily. The encoded receptor has been shown to have increased expression upon T-cell activation, and it is thought to play a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells. Knockout studies in mice also suggest the role of this receptor is in the regulation of CD3-driven T-cell activation and programmed cell death. Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004195.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF18	NM_004195.3	MANE Select	c.664G>T	p.Glu222*	stop_gained	Exon 5 of 5	NP_004186.1	Q9Y5U5-1
	TNFRSF18	NM_148902.2		c.643G>T	p.Glu215*	stop_gained	Exon 5 of 5	NP_683700.1	Q9Y5U5-3
	TNFRSF18	NM_148901.2		c.453G>T	p.Pro151Pro	synonymous	Exon 4 of 4	NP_683699.1	Q9Y5U5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF18	ENST00000379268.7	TSL:1 MANE Select	c.664G>T	p.Glu222*	stop_gained	Exon 5 of 5	ENSP00000368570.2	Q9Y5U5-1
	TNFRSF18	ENST00000379265.5	TSL:1	c.643G>T	p.Glu215*	stop_gained	Exon 5 of 5	ENSP00000368567.5	Q9Y5U5-3
	TNFRSF18	ENST00000486728.5	TSL:1	c.448G>T	p.Glu150*	stop_gained	Exon 4 of 4	ENSP00000462735.1	J3KT02

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455050 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 724026

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 85982

European-Finnish (FIN) AF: 0.0000209 AC: 1 AN: 47852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111428

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.60	D
PhyloP100		3.1
Vest4		0.60
GERP RS		3.3
Mutation Taster		=95/105	disease causing

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: rs756517100; hg19: chr1-1139286;