rs6608

chr17-7561096-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003808.4(TNFSF13):c.*263C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,596,328 control chromosomes in the GnomAD database, including 21,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1890 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20035 hom.)
• Consequence: TNFSF13 NM_003808.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.272

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-7561096-C-T is Benign according to our data. Variant chr17-7561096-C-T is described in ClinVar as [Benign]. Clinvar id is 1230540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF13	NM_003808.4	c.*263C>T		3_prime_UTR_variant	6/6	ENST00000338784.9
TNFSF12-TNFSF13	NM_172089.4	c.*263C>T		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF13	ENST00000338784.9	c.*263C>T		3_prime_UTR_variant	6/6	1	NM_003808.4	P3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23110 AN: 151874 Hom.: 1881 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0523

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.163 AC: 235850 AN: 1444336 Hom.: 20035 Cov.: 29 AF XY: 0.162 AC XY: 116430 AN XY: 719328

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.0717

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.0774

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.152 AC: 23137 AN: 151992 Hom.: 1890 Cov.: 32 AF XY: 0.146 AC XY: 10876 AN XY: 74316

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0524

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.146

Alfa AF: 0.161 Hom.: 2832

Bravo AF: 0.158

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 26. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	14
Dann	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs6608; hg19: chr17-7464413; COSMIC: COSV53433897; COSMIC: COSV53433897;