rs3803800

Variant names:

• chr17-7559652-A-G
• rs3803800
• NM_003808.4:c.287A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7559652-A-G
• chr17-7559652-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (33846 hom., cov: 28)
  • Exomes 𝑓: 0.76 (424631 hom.)
• Consequence: TNFSF13 NM_003808.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.14
• Publications: 123 publications found

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]

TNFSF12-TNFSF13 (HGNC:33537): (TNFSF12-TNFSF13 readthrough) This gene encodes a member of the tumor necrosis factor superfamily. It encodes a hybrid protein composed of the cytoplasmic and transmembrane domains of family member 12 fused to the C-terminal domain of family member 13. The hybrid protein is membrane anchored and presents the receptor-binding domain of family member 13 at the cell surface. It stimulates cycling in T- and B-lymphoma cell lines. [provided by RefSeq, Jul 2008]

ENSG00000276384 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TNFSF13	NM_003808.4	c.287A>G	p.Asn96Ser	missense_variant	Exon 2 of 6	ENST00000338784.9	NP_003799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF13	ENST00000338784.9	c.287A>G	p.Asn96Ser	missense_variant	Exon 2 of 6	1	NM_003808.4	ENSP00000343505.4
TNFSF12-TNFSF13	ENST00000293826.4	c.527A>G	p.Asn176Ser	missense_variant	Exon 7 of 11	1		ENSP00000293826.4

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97085 AN: 151520 Hom.: 33838 Cov.: 28

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

GnomAD2 exomes AF: 0.696 AC: 172329 AN: 247674 AF XY: 0.710

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 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.: 82 AF XY: 0.757 AC XY: 549960 AN XY: 726822

African (AFR) AF: 0.343 AC: 11490 AN: 33476

American (AMR) AF: 0.573 AC: 25566 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 20772 AN: 26118

East Asian (EAS) AF: 0.668 AC: 26522 AN: 39696

South Asian (SAS) AF: 0.662 AC: 57071 AN: 86218

European-Finnish (FIN) AF: 0.756 AC: 40176 AN: 53162

Middle Eastern (MID) AF: 0.765 AC: 4407 AN: 5764

European-Non Finnish (NFE) AF: 0.788 AC: 876420 AN: 1111732

Other (OTH) AF: 0.731 AC: 44110 AN: 60376

GnomAD4 genome AF: 0.640 AC: 97123 AN: 151638 Hom.: 33846 Cov.: 28 AF XY: 0.641 AC XY: 47498 AN XY: 74074

African (AFR) AF: 0.357 AC: 14724 AN: 41294

American (AMR) AF: 0.623 AC: 9477 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2748 AN: 3466

East Asian (EAS) AF: 0.635 AC: 3248 AN: 5114

South Asian (SAS) AF: 0.660 AC: 3156 AN: 4784

European-Finnish (FIN) AF: 0.754 AC: 7940 AN: 10534

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53438 AN: 67906

Other (OTH) AF: 0.669 AC: 1413 AN: 2112

Alfa AF: 0.740 Hom.: 204363

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

Submissions by phenotype

not provided Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22864923) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0024	.;T;.;.;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.57	D
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	T
MutationAssessor	Benign	0.40	.;.;.;N;N;N
PhyloP100		1.1
PrimateAI	Benign	0.31	T
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	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.070
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3803800; hg19: chr17-7462969; COSMIC: COSV53432713; COSMIC: COSV53432713;