Variant chr13-23660489-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_148957.4(TNFRSF19):c.735C>T(p.Cys245=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,611,804 control chromosomes in the GnomAD database, including 4 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 4 hom. )

Consequence

TNFRSF19
NM_148957.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0002132

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0150

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 13-23660489-C-T is Benign according to our data. Variant chr13-23660489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2643679.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF19	NM_148957.4 linkuse as main transcript	c.735C>T	p.Cys245=	splice_region_variant, synonymous_variant	7/10	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.735C>T	p.Cys245=	splice_region_variant, synonymous_variant	7/10	1	NM_148957.4	ENSP00000248484	P1	Q9NS68-2
TNFRSF19	ENST00000382258.8 linkuse as main transcript	c.735C>T	p.Cys245=	splice_region_variant, synonymous_variant	7/9	1		ENSP00000371693		Q9NS68-1
TNFRSF19	ENST00000382263.3 linkuse as main transcript	c.735C>T	p.Cys245=	splice_region_variant, synonymous_variant	7/10	1		ENSP00000371698	P1	Q9NS68-2
TNFRSF19	ENST00000403372.6 linkuse as main transcript	c.339C>T	p.Cys113=	splice_region_variant, synonymous_variant	5/8	2		ENSP00000385408		Q9NS68-3

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000416

AC:

104

AN:

249752

Hom.:

AF XY:

0.000393

AC XY:

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000759

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.000357

AC:

521

AN:

1459618

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

240

AN XY:

726118

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000296

Gnomad4 OTH exome

AF:

0.000847

GnomAD4 genome

AF:

0.000460

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000624

Hom.:

Bravo

AF:

0.000521

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000764

EpiControl

AF:

0.000773

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TNFRSF19: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.1

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.080

SpliceAI score (max)

0.010

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