Genetic Variant TNFRSF17:p.Thr175Thr (chr16-11967817-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001192.3(TNFRSF17):c.525G>A(p.Thr175Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 1,613,968 control chromosomes in the GnomAD database, including 2,728 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 0.052 ( 334 hom., cov: 32)

Exomes 𝑓: 0.040 ( 2394 hom. )

Consequence

TNFRSF17
NM_001192.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.363

Publications

11 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP7

Synonymous conserved (PhyloP=-0.363 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3 link	c.525G>A	p.Thr175Thr	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.525G>A	p.Thr175Thr	synonymous_variant	Exon 3 of 3	1	NM_001192.3	ENSP00000053243.1		Q02223-1

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7895

AN:

152090

Hom.:

331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0829

Gnomad EAS

AF:

0.0693

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0368

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0479

GnomAD2 exomes

AF:

0.0680

AC:

17092

AN:

251210

AF XY:

0.0598

show subpopulations

Gnomad AFR exome

AF:

0.0603

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.0744

Gnomad EAS exome

AF:

0.0700

Gnomad FIN exome

AF:

0.0402

Gnomad NFE exome

AF:

0.0353

Gnomad OTH exome

AF:

0.0570

GnomAD4 exome

AF:

0.0402

AC:

58825

AN:

1461760

Hom.:

2394

Cov.:

AF XY:

0.0390

AC XY:

28336

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0575

AC:

1924

AN:

33470

American (AMR)

AF:

0.229

AC:

10238

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0751

AC:

1963

AN:

26130

East Asian (EAS)

AF:

0.0882

AC:

3501

AN:

39698

South Asian (SAS)

AF:

0.0184

AC:

1583

AN:

86238

European-Finnish (FIN)

AF:

0.0405

AC:

2161

AN:

53416

Middle Eastern (MID)

AF:

0.0357

AC:

206

AN:

5766

European-Non Finnish (NFE)

AF:

0.0313

AC:

34768

AN:

1111948

Other (OTH)

AF:

0.0411

AC:

2481

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

3099

6198

9296

12395

15494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1468

2936

4404

5872

7340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0519

AC:

7900

AN:

152208

Hom.:

334

Cov.:

AF XY:

0.0531

AC XY:

3948

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0545

AC:

2264

AN:

41554

American (AMR)

AF:

0.134

AC:

2048

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0829

AC:

288

AN:

3472

East Asian (EAS)

AF:

0.0694

AC:

360

AN:

5186

South Asian (SAS)

AF:

0.0166

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0368

AC:

390

AN:

10602

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2330

AN:

67986

Other (OTH)

AF:

0.0474

AC:

100

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

373

746

1120

1493

1866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0474

Hom.:

278

Bravo

AF:

0.0643

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

EpiCase

AF:

0.0321

EpiControl

AF:

0.0329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.8

(source)

DANN

Benign

0.90

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(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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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