20-63697476-C-G

Variant names:

• chr20-63697476-C-G
• rs1291205
• NM_003823.4:c.573C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.573C>G	p.Thr191Thr	synonymous	Exon 2 of 3	NP_003814.1	O95407
	RTEL1-TNFRSF6B	NR_037882.1		n.5307C>G		non_coding_transcript_exon	Exon 37 of 38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF6B	ENST00000369996.3	TSL:1 MANE Select	c.573C>G	p.Thr191Thr	synonymous	Exon 2 of 3	ENSP00000359013.1	O95407
	RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1912C>G		non_coding_transcript_exon	Exon 34 of 35	ENSP00000457428.1	D6RA96
	RTEL1-TNFRSF6B	ENST00000492259.6	TSL:5	n.*1912C>G		3_prime_UTR	Exon 34 of 35	ENSP00000457428.1	D6RA96

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

GnomAD2 exomes AF: 0.242 AC: 45232 AN: 186830 AF XY: 0.242

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 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

African (AFR) AF: 0.0503 AC: 1650 AN: 32822

American (AMR) AF: 0.239 AC: 9292 AN: 38900

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5781 AN: 25494

East Asian (EAS) AF: 0.619 AC: 23097 AN: 37322

South Asian (SAS) AF: 0.253 AC: 20803 AN: 82336

European-Finnish (FIN) AF: 0.198 AC: 9825 AN: 49700

Middle Eastern (MID) AF: 0.200 AC: 1141 AN: 5712

European-Non Finnish (NFE) AF: 0.242 AC: 265075 AN: 1094072

Other (OTH) AF: 0.249 AC: 14709 AN: 58986

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

African (AFR) AF: 0.0623 AC: 2590 AN: 41544

American (AMR) AF: 0.210 AC: 3218 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3231 AN: 5156

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4830

European-Finnish (FIN) AF: 0.201 AC: 2134 AN: 10596

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15599 AN: 67972

Other (OTH) AF: 0.198 AC: 419 AN: 2112

Alfa AF: 0.216 Hom.: 1302

Bravo AF: 0.192

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.9
DANN	Benign	0.70
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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