rs9314261

Positions:

• chr8-23109925-G-A

Variant summary

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

The NM_003841.5(TNFRSF10C):​c.61-1795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,526 control chromosomes in the GnomAD database, including 9,437 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 0.30 (9437 hom., cov: 28)
• Consequence: TNFRSF10C NM_003841.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF10C	NM_003841.5	c.61-1795G>A		intron_variant		ENST00000356864.4	NP_003832.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF10C	ENST00000356864.4	c.61-1795G>A		intron_variant		1	NM_003841.5	ENSP00000349324	P1
TNFRSF10C	ENST00000517558.1	c.61-4732G>A		intron_variant, NMD_transcript_variant		2		ENSP00000428235

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45268 AN: 151410 Hom.: 9408 Cov.: 28

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.299 AC: 45358 AN: 151526 Hom.: 9437 Cov.: 28 AF XY: 0.303 AC XY: 22425 AN XY: 74048

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.299

Alfa AF: 0.180 Hom.: 3967

Bravo AF: 0.329

Asia WGS AF: 0.408 AC: 1415 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs9314261; hg19: chr8-22967438;