dbSNP rs11466696: TNFRSF18:c.*309G>A (chr1-1203535-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.947

Publications

1 publications found

Variant links:

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]

TNFRSF18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF18	NM_004195.3 link	c.*309G>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000379268.7	NP_004186.1	Q9Y5U5-1
TNFRSF18	NM_148901.2 link	c.*56G>A	3_prime_UTR_variant	Exon 4 of 4		NP_683699.1	Q9Y5U5-2
TNFRSF18	NM_148902.2 link	c.*309G>A	3_prime_UTR_variant	Exon 5 of 5		NP_683700.1	Q9Y5U5-3
TNFRSF18	XM_017002722.3 link	c.*56G>A	3_prime_UTR_variant	Exon 4 of 4		XP_016858211.1	A0A0R7FDM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF18	ENST00000379268.7 link	c.*309G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004195.3	ENSP00000368570.2		Q9Y5U5-1
TNFRSF18	ENST00000328596.10 link	c.*56G>A		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000328207.6		Q9Y5U5-2

Frequencies

GnomAD3 genomes

AF:

0.00813

AC:

1237

AN:

152208

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.000884

AC XY:

552

AN XY:

624218

show subpopulations

African (AFR)

AF:

0.0284

AC:

788

AN:

27716

American (AMR)

AF:

0.00197

AC:

AN:

21802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18524

East Asian (EAS)

AF:

0.00

AC:

AN:

34554

South Asian (SAS)

AF:

0.0000647

AC:

AN:

61788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31384

Middle Eastern (MID)

AF:

0.00307

AC:

AN:

3586

European-Non Finnish (NFE)

AF:

0.000220

AC:

227

AN:

1033536

Other (OTH)

AF:

0.00222

AC:

118

AN:

53270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00819

AC:

1247

AN:

152326

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

586

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0279

AC:

1161

AN:

41574

American (AMR)

AF:

0.00287

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68008

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

129

193

258

322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00680

Hom.:

Bravo

AF:

0.00980

Asia WGS

AF:

0.00318

AC:

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

(source)

DANN

Benign

0.50

PhyloP100

-0.95

Mutation Taster

=100/0

polymorphism

(source)

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

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rs11466696

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over