rs2298213

Variant names:

• chr1-1203822-T-C
• rs2298213
• ENST00000328596.10:c.537A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_148901.2(TNFRSF18):​c.537A>G​(p.Pro179Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0832 in 1,582,584 control chromosomes in the GnomAD database, including 11,179 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 0.17 (4217 hom., cov: 33)
  • Exomes 𝑓: 0.074 (6962 hom.)
• Consequence: TNFRSF18 NM_148901.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 8 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-0.363 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148901.2. 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.*22A>G		3_prime_UTR	Exon 5 of 5	NP_004186.1	Q9Y5U5-1
	TNFRSF18	NM_148901.2		c.537A>G	p.Pro179Pro	synonymous	Exon 4 of 4	NP_683699.1	Q9Y5U5-2
	TNFRSF18	NM_148902.2		c.*22A>G		3_prime_UTR	Exon 5 of 5	NP_683700.1	Q9Y5U5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF18	ENST00000328596.10	TSL:1	c.537A>G	p.Pro179Pro	synonymous	Exon 4 of 4	ENSP00000328207.6	Q9Y5U5-2
	TNFRSF18	ENST00000379268.7	TSL:1 MANE Select	c.*22A>G		3_prime_UTR	Exon 5 of 5	ENSP00000368570.2	Q9Y5U5-1
	TNFRSF18	ENST00000379265.5	TSL:1	c.*22A>G		downstream_gene	N/A	ENSP00000368567.5	Q9Y5U5-3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25608 AN: 152044 Hom.: 4186 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0709

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.0905 AC: 17978 AN: 198568 AF XY: 0.0841

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.0729

Gnomad ASJ exome AF: 0.0856

Gnomad EAS exome AF: 0.121

Gnomad FIN exome AF: 0.0638

Gnomad NFE exome AF: 0.0579

Gnomad OTH exome AF: 0.0863

GnomAD4 exome AF: 0.0741 AC: 105961 AN: 1430422 Hom.: 6962 Cov.: 33 AF XY: 0.0725 AC XY: 51518 AN XY: 710548

African (AFR) AF: 0.458 AC: 15152 AN: 33048

American (AMR) AF: 0.0755 AC: 3177 AN: 42096

Ashkenazi Jewish (ASJ) AF: 0.0869 AC: 2227 AN: 25634

East Asian (EAS) AF: 0.153 AC: 5913 AN: 38556

South Asian (SAS) AF: 0.0677 AC: 5647 AN: 83398

European-Finnish (FIN) AF: 0.0661 AC: 2645 AN: 40028

Middle Eastern (MID) AF: 0.0904 AC: 505 AN: 5586

European-Non Finnish (NFE) AF: 0.0588 AC: 64793 AN: 1102674

Other (OTH) AF: 0.0994 AC: 5902 AN: 59402

GnomAD4 genome AF: 0.169 AC: 25699 AN: 152162 Hom.: 4217 Cov.: 33 AF XY: 0.166 AC XY: 12317 AN XY: 74390

African (AFR) AF: 0.434 AC: 18021 AN: 41494

American (AMR) AF: 0.0948 AC: 1451 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3468

East Asian (EAS) AF: 0.131 AC: 677 AN: 5164

South Asian (SAS) AF: 0.0712 AC: 343 AN: 4820

European-Finnish (FIN) AF: 0.0568 AC: 603 AN: 10616

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3894 AN: 67982

Other (OTH) AF: 0.143 AC: 303 AN: 2114

Alfa AF: 0.0901 Hom.: 419

Bravo AF: 0.184

Asia WGS AF: 0.144 AC: 500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.37
PhyloP100		-0.36
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: rs2298213; hg19: chr1-1139202; COSMIC: COSV60775814; COSMIC: COSV60775814;