rs145921851

Variant names:

• chr8-23114662-C-G
• rs145921851
• ENST00000520607.1:c.-70C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-23114662-C-G
• chr8-23114662-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000520607.1(ENSG00000284956):​c.-70C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: ENSG00000284956 ENST00000520607.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.319
• Publications: 1 publications found

Genes affected

ENSG00000284956 (HGNC:):

TNFRSF10C (HGNC:11906): (TNF receptor superfamily member 10c) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains an extracellular TRAIL-binding domain and a transmembrane domain, but no cytoplasmic death domain. This receptor is not capable of inducing apoptosis, and is thought to function as an antagonistic receptor that protects cells from TRAIL-induced apoptosis. This gene was found to be a p53-regulated DNA damage-inducible gene. The expression of this gene was detected in many normal tissues but not in most cancer cell lines, which may explain the specific sensitivity of cancer cells to the apoptosis-inducing activity of TRAIL. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022176743).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520607.1. 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
	TNFRSF10C	NM_003841.5	MANE Select	c.172C>G	p.His58Asp	missense	Exon 3 of 5	NP_003832.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000284956	ENST00000520607.1	TSL:4	c.-70C>G		5_prime_UTR_premature_start_codon_gain	Exon 5 of 6	ENSP00000493787.1	A0A2R8YDH7
	TNFRSF10C	ENST00000356864.4	TSL:1 MANE Select	c.172C>G	p.His58Asp	missense	Exon 3 of 5	ENSP00000349324.4	O14798
	ENSG00000284956	ENST00000520607.1	TSL:4	c.-70C>G		5_prime_UTR	Exon 5 of 6	ENSP00000493787.1	A0A2R8YDH7

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 79 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00188

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000111 AC: 28 AN: 251218 AF XY: 0.000125

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1460944 Hom.: 0 Cov.: 30 AF XY: 0.0000454 AC XY: 33 AN XY: 726838

African (AFR) AF: 0.00197 AC: 66 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111258

Other (OTH) AF: 0.0000994 AC: 6 AN: 60346

GnomAD4 genome AF: 0.000519 AC: 79 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74476

African (AFR) AF: 0.00188 AC: 78 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000791 Hom.: 0

Bravo AF: 0.000597

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000157 AC: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.32
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.052
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.42
MVP		0.44
MPC		0.038
ClinPred		0.14	T
GERP RS		-2.6
Varity_R		0.17
gMVP		0.79
Mutation Taster		=300/0	polymorphism

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: rs145921851; hg19: chr8-22972175;