dbSNP rs2017662: TNFRSF17:p.Thr159Thr (chr16-11967769-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001192.3(TNFRSF17):c.477G>A(p.Thr159Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,614,082 control chromosomes in the GnomAD database, including 7,062 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 0.12 ( 1489 hom., cov: 32)

Exomes 𝑓: 0.065 ( 5573 hom. )

Consequence

TNFRSF17
NM_001192.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.559

Variant links:

Genes affected

TNFRSF17 (HGNC:11913): (TNF receptor superfamily member 17) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation. [provided by RefSeq, Jul 2008]

TNFRSF17 links:

NPIPB2 (HGNC:37451): (nuclear pore complex interacting protein family member B2) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NPIPB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-0.559 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3 link	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 3	ENST00000053243.6	NP_001183.2	Q02223-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF17	ENST00000053243.6 link	c.477G>A	p.Thr159Thr	synonymous_variant	Exon 3 of 3	1	NM_001192.3	ENSP00000053243.1		Q02223-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17620

AN:

152092

Hom.:

1484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.0305

Gnomad FIN

AF:

0.0872

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0507

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.110

AC:

27756

AN:

251416

Hom.:

2938

AF XY:

0.0969

AC XY:

13161

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.320

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.0312

Gnomad FIN exome

AF:

0.0903

Gnomad NFE exome

AF:

0.0526

Gnomad OTH exome

AF:

0.0875

GnomAD4 exome

AF:

0.0651

AC:

95216

AN:

1461872

Hom.:

5573

Cov.:

AF XY:

0.0630

AC XY:

45783

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.167

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.0918

Gnomad4 NFE exome

AF:

0.0470

Gnomad4 OTH exome

AF:

0.0760

GnomAD4 genome

AF:

0.116

AC:

17648

AN:

152210

Hom.:

1489

Cov.:

AF XY:

0.117

AC XY:

8734

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.0307

Gnomad4 FIN

AF:

0.0872

Gnomad4 NFE

AF:

0.0507

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.0760

Hom.:

941

Bravo

AF:

0.133

Asia WGS

AF:

0.113

AC:

395

AN:

3478

EpiCase

AF:

0.0504

EpiControl

AF:

0.0519

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.58

DANN

Benign

0.91

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over