dbSNP rs373496: TNFRSF17:p.Asn81Ser (chr16-11966306-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001192.3(TNFRSF17):c.242A>G(p.Asn81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,613,932 control chromosomes in the GnomAD database, including 780,504 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.96 ( 70790 hom., cov: 32)

Exomes 𝑓: 0.99 ( 709714 hom. )

Consequence

TNFRSF17
NM_001192.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.805

Publications

38 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0640447E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF17	NM_001192.3 link	c.242A>G	p.Asn81Ser	missense_variant	Exon 2 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.242A>G	p.Asn81Ser	missense_variant	Exon 2 of 3	1	NM_001192.3	ENSP00000053243.1		Q02223-1

Frequencies

GnomAD3 genomes

AF:

0.964

AC:

146602

AN:

152136

Hom.:

70755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

0.998

Gnomad AMR

AF:

0.980

Gnomad ASJ

AF:

0.987

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.975

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.987

Gnomad OTH

AF:

0.979

GnomAD2 exomes

AF:

0.982

AC:

246811

AN:

251354

AF XY:

0.983

show subpopulations

Gnomad AFR exome

AF:

0.901

Gnomad AMR exome

AF:

0.992

Gnomad ASJ exome

AF:

0.988

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.993

Gnomad NFE exome

AF:

0.988

Gnomad OTH exome

AF:

0.985

GnomAD4 exome

AF:

0.985

AC:

1440227

AN:

1461678

Hom.:

709714

Cov.:

AF XY:

0.985

AC XY:

716232

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.900

AC:

30106

AN:

33466

American (AMR)

AF:

0.990

AC:

44273

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.989

AC:

25826

AN:

26126

East Asian (EAS)

AF:

0.999

AC:

39655

AN:

39680

South Asian (SAS)

AF:

0.973

AC:

83910

AN:

86222

European-Finnish (FIN)

AF:

0.990

AC:

52880

AN:

53402

Middle Eastern (MID)

AF:

0.983

AC:

5667

AN:

5766

European-Non Finnish (NFE)

AF:

0.988

AC:

1098547

AN:

1111912

Other (OTH)

AF:

0.983

AC:

59363

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

973

1946

2920

3893

4866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21664

43328

64992

86656

108320

<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:

0.963

AC:

146695

AN:

152254

Hom.:

70790

Cov.:

AF XY:

0.964

AC XY:

71784

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.901

AC:

37409

AN:

41516

American (AMR)

AF:

0.980

AC:

14963

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.987

AC:

3427

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5186

AN:

5190

South Asian (SAS)

AF:

0.975

AC:

4706

AN:

4828

European-Finnish (FIN)

AF:

0.994

AC:

10549

AN:

10612

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.987

AC:

67185

AN:

68046

Other (OTH)

AF:

0.978

AC:

2070

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

262

525

787

1050

1312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.980

Hom.:

211347

Bravo

AF:

0.961

TwinsUK

AF:

0.988

AC:

3665

ALSPAC

AF:

0.991

AC:

3819

ESP6500AA

AF:

0.899

AC:

3951

ESP6500EA

AF:

0.988

AC:

8499

ExAC

AF:

0.979

AC:

118881

Asia WGS

AF:

0.977

AC:

3399

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.097

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.11

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

PhyloP100

-0.81

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.34

REVEL

Benign

0.0040

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.023

MPC

0.0073

ClinPred

0.0083

GERP RS

-3.1

Varity_R

0.037

gMVP

0.093

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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