20-63697476-C-G

Position:

• chr20-63697476-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003823.4(TNFRSF6B):​c.573C>G​(p.Thr191Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,577,530 control chromosomes in the GnomAD database, including 51,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3894 hom., cov: 33)
  • Exomes 𝑓: 0.25 (47615 hom.)
• Consequence: TNFRSF6B NM_003823.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.106

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 20-63697476-C-G is Benign according to our data. Variant chr20-63697476-C-G is described in ClinVar as [Benign]. Clinvar id is 1169888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.106 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF6B	NM_003823.4	c.573C>G	p.Thr191Thr	synonymous_variant	2/3	ENST00000369996.3	NP_003814.1
RTEL1-TNFRSF6B	NR_037882.1	n.5307C>G		non_coding_transcript_exon_variant	37/38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF6B	ENST00000369996.3	c.573C>G	p.Thr191Thr	synonymous_variant	2/3	1	NM_003823.4	ENSP00000359013.1
RTEL1-TNFRSF6B	ENST00000492259.6	n.*1912C>G		non_coding_transcript_exon_variant	34/35	5		ENSP00000457428.1
RTEL1-TNFRSF6B	ENST00000492259.6	n.*1912C>G		3_prime_UTR_variant	34/35	5		ENSP00000457428.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29533 AN: 152068 Hom.: 3897 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.242 AC: 45232 AN: 186830 Hom.: 6746 AF XY: 0.242 AC XY: 24425 AN XY: 100898

Gnomad AFR exome AF: 0.0551

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.625

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.247 AC: 351373 AN: 1425344 Hom.: 47615 Cov.: 39 AF XY: 0.247 AC XY: 174117 AN XY: 705996

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.198

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.194 AC: 29532 AN: 152186 Hom.: 3894 Cov.: 33 AF XY: 0.197 AC XY: 14622 AN XY: 74390

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.198

Alfa AF: 0.216 Hom.: 1302

Bravo AF: 0.192

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.65
CADD	Benign	5.9
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs1291205; hg19: chr20-62328829; COSMIC: COSV53927498; COSMIC: COSV53927498;