Variant chr8-23114694-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000520607(ENSG00000284956):c.-38G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,612,984 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 12 hom. )

Consequence

ENSG00000284956
ENST00000520607 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: -6.38

Variant links:

Genes affected

ENSG00000284956 (HGNC:):

ENSG00000284956 links:

TNFRSF10C (HGNC:11906): (TNF receptor superfamily member 10c) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. [provided by RefSeq, Jul 2008]

TNFRSF10C 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=-0.9).

BP6

Variant 8-23114694-G-A is Benign according to our data. Variant chr8-23114694-G-A is described in ClinVar as [Benign]. Clinvar id is 709419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00796 (1209/151836) while in subpopulation AFR AF= 0.0162 (665/41174). AF 95% confidence interval is 0.0151. There are 2 homozygotes in gnomad4. There are 588 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5 linkuse as main transcript	c.204G>A	p.Pro68Pro	synonymous_variant	3/5	ENST00000356864.4	NP_003832.3	O14798

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ENSG00000284956	ENST00000520607 linkuse as main transcript	c.-38G>A		5_prime_UTR_premature_start_codon_gain_variant	5/6	4		ENSP00000493787.1	A0A2R8YDH7
TNFRSF10C	ENST00000356864.4 linkuse as main transcript	c.204G>A	p.Pro68Pro	synonymous_variant	3/5	1	NM_003841.5	ENSP00000349324.4	O14798
ENSG00000284956	ENST00000520607 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	5/6	4		ENSP00000493787.1	A0A2R8YDH7

Frequencies

GnomAD3 genomes

AF:

0.00789

AC:

1197

AN:

151720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00518

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00735

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00272

AC:

685

AN:

251482

Hom.:

AF XY:

0.00274

AC XY:

373

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00628

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00377

AC:

5512

AN:

1461148

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

2686

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.000659

Gnomad4 AMR exome

AF:

0.00172

Gnomad4 ASJ exome

AF:

0.00134

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00577

Gnomad4 NFE exome

AF:

0.00439

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00796

AC:

1209

AN:

151836

Hom.:

Cov.:

AF XY:

0.00792

AC XY:

588

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0162

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.0113

Gnomad4 FIN

AF:

0.00735

Gnomad4 NFE

AF:

0.00431

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00406

Hom.:

EpiCase

AF:

0.00425

EpiControl

AF:

0.00302

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

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