chr17-7559652-A-G

Position:

chr17-7559652-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003808.4(TNFSF13):c.287A>G(p.Asn96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,612,798 control chromosomes in the GnomAD database, including 458,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.64 ( 33846 hom., cov: 28)

Exomes 𝑓: 0.76 ( 424631 hom. )

Consequence

TNFSF13
NM_003808.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

TNFSF13 (HGNC:11928): (TNF superfamily member 13) The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM. Alternative splicing results in multiple transcript variants. Some transcripts that skip the last exon of the upstream gene (TNFSF12) and continue into the second exon of this gene have been identified; such read-through transcripts are contained in GeneID 407977, TNFSF12-TNFSF13. [provided by RefSeq, Oct 2010]

TNFSF13 links:

TNFSF12-TNFSF13 (HGNC:):

TNFSF12-TNFSF13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2001234E-6).

BP6

Variant 17-7559652-A-G is Benign according to our data. Variant chr17-7559652-A-G is described in ClinVar as [Benign]. Clinvar id is 1270041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13	NM_003808.4 linkuse as main transcript	c.287A>G	p.Asn96Ser	missense_variant	2/6	ENST00000338784.9	NP_003799.1
TNFSF12-TNFSF13	NM_172089.4 linkuse as main transcript	c.527A>G	p.Asn176Ser	missense_variant	7/11		NP_742086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13	ENST00000338784.9 linkuse as main transcript	c.287A>G	p.Asn96Ser	missense_variant	2/6	1	NM_003808.4	ENSP00000343505	P3	O75888-1

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97085

AN:

151520

Hom.:

33838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.793

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.754

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.676

GnomAD3 exomes

AF:

0.696

AC:

172329

AN:

247674

Hom.:

61948

AF XY:

0.710

AC XY:

95181

AN XY:

134044

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.796

Gnomad EAS exome

AF:

0.631

Gnomad SAS exome

AF:

0.661

Gnomad FIN exome

AF:

0.754

Gnomad NFE exome

AF:

0.785

Gnomad OTH exome

AF:

0.743

GnomAD4 exome

AF:

0.757

AC:

1106534

AN:

1461160

Hom.:

424631

Cov.:

AF XY:

0.757

AC XY:

549960

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.573

Gnomad4 ASJ exome

AF:

0.795

Gnomad4 EAS exome

AF:

0.668

Gnomad4 SAS exome

AF:

0.662

Gnomad4 FIN exome

AF:

0.756

Gnomad4 NFE exome

AF:

0.788

Gnomad4 OTH exome

AF:

0.731

GnomAD4 genome

AF:

0.640

AC:

97123

AN:

151638

Hom.:

33846

Cov.:

AF XY:

0.641

AC XY:

47498

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.623

Gnomad4 ASJ

AF:

0.793

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.754

Gnomad4 NFE

AF:

0.787

Gnomad4 OTH

AF:

0.669

Alfa

AF:

0.760

Hom.:

109469

Bravo

AF:

0.620

TwinsUK

AF:

0.795

AC:

2949

ALSPAC

AF:

0.800

AC:

3085

ESP6500AA

AF:

0.377

AC:

1663

ESP6500EA

AF:

0.785

AC:

6749

ExAC

AF:

0.694

AC:

84245

Asia WGS

AF:

0.569

AC:

1979

AN:

3478

EpiCase

AF:

0.799

EpiControl

AF:

0.796

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	This variant is associated with the following publications: (PMID: 22864923) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0024

.;T;.;.;T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.71

T;T;T;T;T;T

MetaRNN

Benign

0.0000012

T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.40

.;.;.;N;N;N

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.47

N;N;N;N;N;N

REVEL

Benign

0.29

Sift

Benign

0.33

T;T;T;T;T;T

Sift4G

Benign

0.48

T;T;T;T;T;T

Polyphen

0.0020, 0.0, 0.0010

.;.;.;B;B;B

Vest4

0.026

MPC

0.45

ClinPred

0.0084

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over