Variant chr17-7559617-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000338784.9(TNFSF13):c.259-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,612,926 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 12 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 11 hom. )

Consequence

TNFSF13
ENST00000338784.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005724

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.554

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-7559617-T-C is Benign according to our data. Variant chr17-7559617-T-C is described in ClinVar as [Benign]. Clinvar id is 780064.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-7559617-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0072 (1094/151924) while in subpopulation AFR AF= 0.0243 (1006/41418). AF 95% confidence interval is 0.023. There are 12 homozygotes in gnomad4. There are 508 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF13	NM_003808.4 linkuse as main transcript	c.259-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000338784.9	NP_003799.1
TNFSF12-TNFSF13	NM_172089.4 linkuse as main transcript	c.499-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_742086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF13	ENST00000338784.9 linkuse as main transcript	c.259-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003808.4	ENSP00000343505	P3	O75888-1

Frequencies

GnomAD3 genomes

AF:

0.00717

AC:

1089

AN:

151806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00407

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00198

AC:

490

AN:

247724

Hom.:

AF XY:

0.00132

AC XY:

177

AN XY:

134052

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.00183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.000243

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.000735

AC:

1074

AN:

1461002

Hom.:

Cov.:

AF XY:

0.000600

AC XY:

436

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.0218

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00720

AC:

1094

AN:

151924

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

508

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00333

Hom.:

Bravo

AF:

0.00824

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000057

dbscSNV1_RF

Benign

0.0

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

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