rs11466696

Positions:

• chr1-1203535-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004195.3(TNFRSF18):​c.*309G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,438,486 control chromosomes in the GnomAD database, including 32 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 0.0082 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00093 (18 hom.)
• Consequence: TNFRSF18 NM_004195.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00819 (1247/152326) while in subpopulation AFR AF= 0.0279 (1161/41574). AF 95% confidence interval is 0.0266. There are 14 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF18	NM_004195.3	c.*309G>A		3_prime_UTR_variant	5/5	ENST00000379268.7	NP_004186.1
TNFRSF18	NM_148901.2	c.*56G>A		3_prime_UTR_variant	4/4		NP_683699.1
TNFRSF18	NM_148902.2	c.*309G>A		3_prime_UTR_variant	5/5		NP_683700.1
TNFRSF18	XM_017002722.3	c.*56G>A		3_prime_UTR_variant	4/4		XP_016858211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF18	ENST00000379268.7	c.*309G>A		3_prime_UTR_variant	5/5	1	NM_004195.3	ENSP00000368570	A2
TNFRSF18	ENST00000328596.10	c.*56G>A		3_prime_UTR_variant	4/4	1		ENSP00000328207

Frequencies

GnomAD3 genomes AF: 0.00813 AC: 1237 AN: 152208 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00862

GnomAD4 exome AF: 0.000926 AC: 1191 AN: 1286160 Hom.: 18 Cov.: 31 AF XY: 0.000884 AC XY: 552 AN XY: 624218

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000647

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000220

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00819 AC: 1247 AN: 152326 Hom.: 14 Cov.: 33 AF XY: 0.00787 AC XY: 586 AN XY: 74486

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.00680 Hom.: 2

Bravo AF: 0.00980

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs11466696; hg19: chr1-1138915;