rs1291206

Positions:

• chr20-63697816-G-A
• chr20-63697816-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003823.4(TNFRSF6B):​c.619+294G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,086 control chromosomes in the GnomAD database, including 3,874 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3874 hom., cov: 32)
• Consequence: TNFRSF6B NM_003823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF6B	NM_003823.4	c.619+294G>A		intron_variant		ENST00000369996.3
RTEL1-TNFRSF6B	NR_037882.1	n.5353+294G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF6B	ENST00000369996.3	c.619+294G>A		intron_variant		1	NM_003823.4	P1
RTEL1-TNFRSF6B	ENST00000697815.1	n.3273+294G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29487 AN: 151968 Hom.: 3877 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29486 AN: 152086 Hom.: 3874 Cov.: 32 AF XY: 0.196 AC XY: 14605 AN XY: 74346

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.199

Alfa AF: 0.193 Hom.: 413

Bravo AF: 0.192

Asia WGS AF: 0.404 AC: 1405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.0
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs1291206; hg19: chr20-62329169;