8-23104835-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-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

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.485

Alfa AF: 0.398 Hom.: 15375

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4077341; hg19: chr8-22962348;