chr17-7561096-C-T

Variant names:

• chr17-7561096-C-T
• rs6608
• NM_003808.4:c.*263C>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.*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:3
• 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: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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFSF13	NM_003808.4	c.*263C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000338784.9	NP_003799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF13	ENST00000338784.9	c.*263C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_003808.4	ENSP00000343505.4
TNFSF12-TNFSF13	ENST00000293826.4	c.*263C>T		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000293826.4

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 AC: 5800 AN: 33056

Gnomad4 AMR exome AF: 0.100 AC: 4452 AN: 44510

Gnomad4 ASJ exome AF: 0.184 AC: 4754 AN: 25824

Gnomad4 EAS exome AF: 0.0717 AC: 2841 AN: 39596

Gnomad4 SAS exome AF: 0.146 AC: 12527 AN: 85698

Gnomad4 FIN exome AF: 0.0774 AC: 4015 AN: 51890

Gnomad4 NFE exome AF: 0.174 AC: 190898 AN: 1098248

Gnomad4 Remaining exome AF: 0.165 AC: 9881 AN: 59792

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 AC: 0.173861 AN: 0.173861

Gnomad4 AMR AF: 0.126 AC: 0.126063 AN: 0.126063

Gnomad4 ASJ AF: 0.187 AC: 0.186563 AN: 0.186563

Gnomad4 EAS AF: 0.0524 AC: 0.0524178 AN: 0.0524178

Gnomad4 SAS AF: 0.157 AC: 0.157404 AN: 0.157404

Gnomad4 FIN AF: 0.0644 AC: 0.064434 AN: 0.064434

Gnomad4 NFE AF: 0.164 AC: 0.164494 AN: 0.164494

Gnomad4 OTH AF: 0.146 AC: 0.145972 AN: 0.145972

Alfa AF: 0.160 Hom.: 3759

Bravo AF: 0.158

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.83
Mutation Taster		=100/0	polymorphism (auto)

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;