chr20-63696775-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003823.4(TNFRSF6B):c.8C>T(p.Ala3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000529 in 1,587,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

TNFRSF6B
NM_003823.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.236

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05271697).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003823.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF6B	NM_003823.4	MANE Select	c.8C>T	p.Ala3Val	missense	Exon 1 of 3	NP_003814.1	O95407
	RTEL1-TNFRSF6B	NR_037882.1		n.4742C>T		non_coding_transcript_exon	Exon 36 of 38

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TNFRSF6B	ENST00000369996.3	TSL:1 MANE Select	c.8C>T	p.Ala3Val	missense	Exon 1 of 3	ENSP00000359013.1	O95407
RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1347C>T		non_coding_transcript_exon	Exon 33 of 35	ENSP00000457428.1	D6RA96
RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1347C>T		3_prime_UTR	Exon 33 of 35	ENSP00000457428.1	D6RA96

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000417

AC:

AN:

215800

AF XY:

0.0000337

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000637

Gnomad OTH exome

AF:

0.000187

GnomAD4 exome

AF:

0.0000564

AC:

AN:

1435554

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

711270

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

33046

American (AMR)

AF:

0.0000233

AC:

AN:

43006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24688

East Asian (EAS)

AF:

0.00

AC:

AN:

39298

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.0000665

AC:

AN:

1098374

Other (OTH)

AF:

0.0000846

AC:

AN:

59132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000605

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000671

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.45

M_CAP

Benign

0.016

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PhyloP100

0.24

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.52

REVEL

Benign

0.045

Sift

Uncertain

0.026

Sift4G

Pathogenic

0.0

Polyphen

0.0020

Vest4

0.13

MutPred

0.18

Gain of sheet (P = 0.0125)

MVP

0.12

MPC

0.014

ClinPred

0.045

GERP RS

0.069

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.028

gMVP

0.57

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over