8-23104835-T-G

Variant names:

• chr8-23104835-T-G
• rs4077341
• NM_003841.5:c.60+1654T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003841.5(TNFRSF10C):​c.60+1654T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,028 control chromosomes in the GnomAD database, including 24,274 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 0.53 (24274 hom., cov: 32)
• Consequence: TNFRSF10C NM_003841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 24 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5	c.60+1654T>G		intron_variant	Intron 1 of 4	ENST00000356864.4	NP_003832.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10C	ENST00000356864.4	c.60+1654T>G		intron_variant	Intron 1 of 4	1	NM_003841.5	ENSP00000349324.4
ENSG00000284956	ENST00000520607.1	c.-182+4151T>G		intron_variant	Intron 3 of 5	4		ENSP00000493787.1
TNFRSF10C	ENST00000517558.1	n.60+1654T>G		intron_variant	Intron 1 of 3	2		ENSP00000428235.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80471 AN: 151910 Hom.: 24224 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.530 AC: 80585 AN: 152028 Hom.: 24274 Cov.: 32 AF XY: 0.532 AC XY: 39524 AN XY: 74294

African (AFR) AF: 0.789 AC: 32698 AN: 41460

American (AMR) AF: 0.588 AC: 8990 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3468

East Asian (EAS) AF: 0.752 AC: 3891 AN: 5176

South Asian (SAS) AF: 0.551 AC: 2653 AN: 4812

European-Finnish (FIN) AF: 0.357 AC: 3774 AN: 10568

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25941 AN: 67942

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.418 Hom.: 22023

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.83
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4077341; hg19: chr8-22962348;