rs2241063

chr3-172512081-G-T

Variant summary

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

The NM_003810.4(TNFSF10):c.271-422C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,150 control chromosomes in the GnomAD database, including 3,312 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 0.18 (3312 hom., cov: 32)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

Genes affected

TNFSF10 (HGNC:11925): (TNF superfamily member 10) The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein preferentially induces apoptosis in transformed and tumor cells, but does not appear to kill normal cells although it is expressed at a significant level in most normal tissues. This protein binds to several members of TNF receptor superfamily including TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and possibly also to TNFRSF11B/OPG. The activity of this protein may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4, and TNFRSF11B/OPG that cannot induce apoptosis. The binding of this protein to its receptors has been shown to trigger the activation of MAPK8/JNK, caspase 8, and caspase 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF10	NM_003810.4	c.271-422C>A		intron_variant		ENST00000241261.7
TNFSF10	NM_001190942.2	c.270+2780C>A		intron_variant
TNFSF10	NR_033994.2	n.317-2760C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF10	ENST00000241261.7	c.271-422C>A		intron_variant		1	NM_003810.4	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27527 AN: 152032 Hom.: 3310 Cov.: 32

Gnomad AFR AF: 0.0424

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.181 AC: 27534 AN: 152150 Hom.: 3312 Cov.: 32 AF XY: 0.188 AC XY: 13979 AN XY: 74378

Gnomad4 AFR AF: 0.0423

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.184

Alfa AF: 0.202 Hom.: 582

Bravo AF: 0.166

Asia WGS AF: 0.391 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.3
Dann	Benign	0.51

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: rs2241063; hg19: chr3-172229871;