rs750734718

Variant names:

• chr20-63696822-C-G
• rs750734718
• NM_003823.4:c.55C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-63696822-C-G
• chr20-63696822-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003823.4(TNFRSF6B):​c.55C>G​(p.Pro19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TNFRSF6B NM_003823.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046904147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF6B	NM_003823.4	c.55C>G	p.Pro19Ala	missense_variant	Exon 1 of 3	ENST00000369996.3	NP_003814.1
RTEL1-TNFRSF6B	NR_037882.1	n.4789C>G		non_coding_transcript_exon_variant	Exon 36 of 38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF6B	ENST00000369996.3	c.55C>G	p.Pro19Ala	missense_variant	Exon 1 of 3	1	NM_003823.4	ENSP00000359013.1
RTEL1-TNFRSF6B	ENST00000492259.6	n.*1394C>G		non_coding_transcript_exon_variant	Exon 33 of 35	5		ENSP00000457428.1
RTEL1-TNFRSF6B	ENST00000492259.6	n.*1394C>G		3_prime_UTR_variant	Exon 33 of 35	5		ENSP00000457428.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457416 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724762

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.8
DANN	Benign	0.86
DEOGEN2	Benign	0.085	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.046
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.010	B
Vest4		0.17
MutPred		0.46		Gain of helix (P = 0.0082);
MVP		0.19
MPC		0.014
ClinPred		0.037	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.38

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: rs750734718; hg19: chr20-62328175;