8-23111578-T-C

Variant names:

• chr8-23111578-T-C
• rs10111172
• NM_003841.5:c.61-142T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003841.5. 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.61-142T>C		intron	N/A	NP_003832.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10C	ENST00000356864.4	TSL:1 MANE Select	c.61-142T>C		intron	N/A	ENSP00000349324.4	O14798
	ENSG00000284956	ENST00000520607.1	TSL:4	c.-181-142T>C		intron	N/A	ENSP00000493787.1	A0A2R8YDH7
	TNFRSF10C	ENST00000877636.1		c.61-142T>C		intron	N/A	ENSP00000547695.1

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

African (AFR) AF: 0.912 AC: 12795 AN: 14026

American (AMR) AF: 0.908 AC: 23885 AN: 26318

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 12452 AN: 16222

East Asian (EAS) AF: 0.812 AC: 24593 AN: 30274

South Asian (SAS) AF: 0.846 AC: 45166 AN: 53404

European-Finnish (FIN) AF: 0.768 AC: 34411 AN: 44814

Middle Eastern (MID) AF: 0.857 AC: 3235 AN: 3774

European-Non Finnish (NFE) AF: 0.819 AC: 258762 AN: 316032

Other (OTH) AF: 0.830 AC: 23822 AN: 28686

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

African (AFR) AF: 0.910 AC: 37371 AN: 41058

American (AMR) AF: 0.886 AC: 13509 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2677 AN: 3468

East Asian (EAS) AF: 0.816 AC: 4198 AN: 5146

South Asian (SAS) AF: 0.840 AC: 4028 AN: 4798

European-Finnish (FIN) AF: 0.778 AC: 8106 AN: 10422

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55457 AN: 67948

Other (OTH) AF: 0.849 AC: 1787 AN: 2106

Alfa AF: 0.829 Hom.: 94997

Asia WGS AF: 0.845 AC: 2939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10111172; hg19: chr8-22969091;