chr3-172508962-A-C

Variant names:

• chr3-172508962-A-C
• rs3136598
• NM_003810.4:c.418+255T>G

Variant summary

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

The NM_003810.4(TNFSF10):​c.418+255T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,626 control chromosomes in the GnomAD database, including 37,141 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 0.70 (37141 hom., cov: 30)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.418+255T>G		intron_variant	Intron 4 of 4	ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.271-2043T>G		intron_variant	Intron 2 of 2		NP_001177871.1
TNFSF10	NR_033994.2	n.421+255T>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.418+255T>G		intron_variant	Intron 4 of 4	1	NM_003810.4	ENSP00000241261.2
TNFSF10	ENST00000420541.6	c.271-2043T>G		intron_variant	Intron 2 of 2	1		ENSP00000389931.2
TNFSF10	ENST00000430881.1	n.*78+255T>G		intron_variant	Intron 3 of 3	5		ENSP00000404008.1
TNFSF10	ENST00000494851.5	n.*184T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105498 AN: 151506 Hom.: 37122 Cov.: 30

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.696 AC: 105565 AN: 151626 Hom.: 37141 Cov.: 30 AF XY: 0.694 AC XY: 51385 AN XY: 74084

African (AFR) AF: 0.778 AC: 32149 AN: 41304

American (AMR) AF: 0.569 AC: 8664 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2515 AN: 3466

East Asian (EAS) AF: 0.673 AC: 3465 AN: 5152

South Asian (SAS) AF: 0.633 AC: 3052 AN: 4818

European-Finnish (FIN) AF: 0.702 AC: 7343 AN: 10458

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45950 AN: 67892

Other (OTH) AF: 0.706 AC: 1481 AN: 2098

Alfa AF: 0.679 Hom.: 15156

Bravo AF: 0.689

Asia WGS AF: 0.666 AC: 2315 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	6.4
DANN	Benign	0.57
PhyloP100		0.63
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: rs3136598; hg19: chr3-172226752;