8-23111578-T-C

Position:

• chr8-23111578-T-C

Variant summary

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

The NM_003841.5(TNFRSF10C):​c.61-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 684,948 control chromosomes in the GnomAD database, including 235,602 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 0.85 (54430 hom., cov: 29)
  • Exomes 𝑓: 0.82 (181172 hom.)
• Consequence: TNFRSF10C NM_003841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

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]

ENSG00000284956 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5	c.61-142T>C		intron_variant		ENST00000356864.4	NP_003832.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10C	ENST00000356864.4	c.61-142T>C		intron_variant		1	NM_003841.5	ENSP00000349324.4
ENSG00000284956	ENST00000520607.1	c.-181-142T>C		intron_variant		4		ENSP00000493787.1
TNFRSF10C	ENST00000517558.1	n.61-3079T>C		intron_variant		2		ENSP00000428235.1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128002 AN: 151288 Hom.: 54384 Cov.: 29

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.850

GnomAD4 exome AF: 0.823 AC: 439121 AN: 533550 Hom.: 181172 AF XY: 0.824 AC XY: 234659 AN XY: 284950

Gnomad4 AFR exome AF: 0.912

Gnomad4 AMR exome AF: 0.908

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.846

Gnomad4 FIN exome AF: 0.768

Gnomad4 NFE exome AF: 0.819

Gnomad4 OTH exome AF: 0.830

GnomAD4 genome AF: 0.846 AC: 128102 AN: 151398 Hom.: 54430 Cov.: 29 AF XY: 0.846 AC XY: 62587 AN XY: 73970

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.849

Alfa AF: 0.825 Hom.: 67482

Asia WGS AF: 0.845 AC: 2939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10111172; hg19: chr8-22969091;