Variant chr13-23593341-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_148957.4(TNFRSF19):c.70-4T>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 0.0984 in 1,531,868 control chromosomes in the GnomAD database, including 8,411 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 0.078 ( 687 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7724 hom. )

Consequence

TNFRSF19
NM_148957.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002916

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.564

Variant links:

Genes affected

TNFRSF19 (HGNC:11915): (TNF receptor superfamily member 19) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is highly expressed during embryonic development. It has been shown to interact with TRAF family members, and to activate JNK signaling pathway when overexpressed in cells. This receptor is capable of inducing apoptosis by a caspase-independent mechanism, and it is thought to play an essential role in embryonic development. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

TNFRSF19 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 13-23593341-T-C is Benign according to our data. Variant chr13-23593341-T-C is described in ClinVar as [Benign]. Clinvar id is 770615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF19	NM_148957.4 linkuse as main transcript	c.70-4T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000248484.9	NP_683760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF19	ENST00000248484.9 linkuse as main transcript	c.70-4T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_148957.4	ENSP00000248484	P1	Q9NS68-2

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11927

AN:

152090

Hom.:

687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0641

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.0780

GnomAD3 exomes

AF:

0.0994

AC:

19952

AN:

200636

Hom.:

1349

AF XY:

0.103

AC XY:

11316

AN XY:

110004

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.0441

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.0747

Gnomad NFE exome

AF:

0.0994

Gnomad OTH exome

AF:

0.0915

GnomAD4 exome

AF:

0.101

AC:

138794

AN:

1379660

Hom.:

7724

Cov.:

AF XY:

0.102

AC XY:

69445

AN XY:

683648

show subpopulations

Gnomad4 AFR exome

AF:

0.0135

Gnomad4 AMR exome

AF:

0.0487

Gnomad4 ASJ exome

AF:

0.0458

Gnomad4 EAS exome

AF:

0.217

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.0800

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0784

AC:

11931

AN:

152208

Hom.:

687

Cov.:

AF XY:

0.0780

AC XY:

5800

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.0642

Gnomad4 ASJ

AF:

0.0441

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.0706

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.0781

Alfa

AF:

0.0883

Hom.:

334

Bravo

AF:

0.0745

Asia WGS

AF:

0.191

AC:

664

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.8

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000029

dbscSNV1_RF

Benign

0.010

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