rs2241063

Variant names:

• chr3-172512081-G-T
• rs2241063
• NM_003810.4:c.271-422C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003810.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	NM_003810.4	MANE Select	c.271-422C>A		intron	N/A	NP_003801.1
	TNFSF10	NM_001190942.2		c.270+2780C>A		intron	N/A	NP_001177871.1
	TNFSF10	NR_033994.2		n.317-2760C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFSF10	ENST00000241261.7	TSL:1 MANE Select	c.271-422C>A		intron	N/A	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.270+2780C>A		intron	N/A	ENSP00000389931.2
	TNFSF10	ENST00000430881.1	TSL:5	n.196-2760C>A		intron	N/A	ENSP00000404008.1

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

African (AFR) AF: 0.0423 AC: 1758 AN: 41544

American (AMR) AF: 0.175 AC: 2680 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2194 AN: 5172

South Asian (SAS) AF: 0.324 AC: 1564 AN: 4820

European-Finnish (FIN) AF: 0.296 AC: 3126 AN: 10578

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14686 AN: 67966

Other (OTH) AF: 0.184 AC: 388 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.51
PhyloP100		0.084
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241063; hg19: chr3-172229871;