rs200096730

Variant names:

• chr1-1203940-C-A
• ENST00000328596.10:c.419G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-1203940-C-A
• chr1-1203940-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_148901.2(TNFRSF18):​c.419G>T​(p.Arg140Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNFRSF18 NM_148901.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078680485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF18	NM_004195.3	c.630G>T	p.Pro210Pro	synonymous_variant	Exon 5 of 5	ENST00000379268.7	NP_004186.1
TNFRSF18	NM_148901.2	c.419G>T	p.Arg140Leu	missense_variant	Exon 4 of 4		NP_683699.1
TNFRSF18	XM_017002722.3	c.695G>T	p.Arg232Leu	missense_variant	Exon 4 of 4		XP_016858211.1
TNFRSF18	NM_148902.2	c.609G>T	p.Pro203Pro	synonymous_variant	Exon 5 of 5		NP_683700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF18	ENST00000328596.10	c.419G>T	p.Arg140Leu	missense_variant	Exon 4 of 4	1		ENSP00000328207.6
TNFRSF18	ENST00000379268.7	c.630G>T	p.Pro210Pro	synonymous_variant	Exon 5 of 5	1	NM_004195.3	ENSP00000368570.2
TNFRSF18	ENST00000379265.5	c.609G>T	p.Pro203Pro	synonymous_variant	Exon 5 of 5	1		ENSP00000368567.5
TNFRSF18	ENST00000486728.5	c.414G>T	p.Pro138Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000462735.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454898 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000208

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.41
DANN	Benign	0.72
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.011
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.36	T
Polyphen		0.33	B
Vest4		0.21
MutPred		0.28		Gain of sheet (P = 0.0043);
MVP		0.081
MPC		0.028
ClinPred		0.59	D
GERP RS		-4.3
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1139320;