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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001192.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF17	NM_001192.3	MANE Select	c.242A>G	p.Asn81Ser	missense	Exon 2 of 3	NP_001183.2
NPIPB2	NM_001395854.1		c.-536-2280T>C		intron	N/A	NP_001382783.1	A0A5F9ZI19
NPIPB2	NM_001395855.1		c.-400-10069T>C		intron	N/A	NP_001382784.1	A0A5F9ZI19

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF17	ENST00000053243.6	TSL:1 MANE Select	c.242A>G	p.Asn81Ser	missense	Exon 2 of 3	ENSP00000053243.1	Q02223-1
TNFRSF17	ENST00000562385.1	TSL:1	c.215A>G	p.Asn72Ser	missense	Exon 2 of 4	ENSP00000454314.1	H3BMB5
TNFRSF17	ENST00000396495.3	TSL:1	c.130+852A>G		intron	N/A	ENSP00000379753.3	Q02223-2

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over