Variant chr20-63696914-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003823.4(TNFRSF6B):c.147C>T(p.Cys49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,608,974 control chromosomes in the GnomAD database, including 52,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3883 hom., cov: 34)

Exomes 𝑓: 0.25 ( 49069 hom. )

Consequence

TNFRSF6B
NM_003823.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.886

Variant links:

Genes affected

TNFRSF6B (HGNC:11921): (TNF receptor superfamily member 6b) This gene belongs to the tumor necrosis factor receptor superfamily. The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death. It acts as a decoy receptor that competes with death receptors for ligand binding. Over-expression of this gene has been noted in gastrointestinal tract tumors. Read-through transcription into this gene from the neighboring upstream gene, which encodes regulator of telomere elongation helicase 1 (RTEL1), generates a non-coding transcript. [provided by RefSeq, Feb 2011]

TNFRSF6B links:

RTEL1-TNFRSF6B (HGNC:44095): (RTEL1-TNFRSF6B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RTEL1 (regulator of telomere elongation helicase 1) and TNFRSF6B (tumor necrosis factor receptor superfamily, member 6b, decoy) genes on chromosome 20. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

RTEL1-TNFRSF6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

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

BP6

Variant 20-63696914-C-T is Benign according to our data. Variant chr20-63696914-C-T is described in ClinVar as [Benign]. Clinvar id is 1169885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.886 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF6B	NM_003823.4 linkuse as main transcript	c.147C>T	p.Cys49=	synonymous_variant	1/3	ENST00000369996.3
RTEL1-TNFRSF6B	NR_037882.1 linkuse as main transcript	n.4881C>T		non_coding_transcript_exon_variant	36/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF6B	ENST00000369996.3 linkuse as main transcript	c.147C>T	p.Cys49=	synonymous_variant	1/3	1	NM_003823.4	P1
RTEL1-TNFRSF6B	ENST00000697815.1 linkuse as main transcript	n.2801C>T		non_coding_transcript_exon_variant	13/15

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29483

AN:

152104

Hom.:

3886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0622

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.253

AC:

58764

AN:

232054

Hom.:

9200

AF XY:

0.252

AC XY:

32229

AN XY:

127782

show subpopulations

Gnomad AFR exome

AF:

0.0560

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.643

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.247

AC:

360526

AN:

1456752

Hom.:

49069

Cov.:

AF XY:

0.248

AC XY:

179419

AN XY:

724452

show subpopulations

Gnomad4 AFR exome

AF:

0.0506

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.623

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.194

AC:

29482

AN:

152222

Hom.:

3883

Cov.:

AF XY:

0.196

AC XY:

14607

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0621

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.625

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.216

Hom.:

1278

Bravo

AF:

0.192

Asia WGS

AF:

0.402

AC:

1395

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.75

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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