chr3-172509409-C-T

Variant names:

• chr3-172509409-C-T
• rs3815496
• NM_003810.4:c.314-88G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003810.4(TNFSF10):​c.314-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 967,966 control chromosomes in the GnomAD database, including 226,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (37239 hom., cov: 32)
  • Exomes 𝑓: 0.68 (189400 hom.)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.595
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-172509409-C-T is Benign according to our data. Variant chr3-172509409-C-T is described in ClinVar as Benign. ClinVar VariationId is 1174337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 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.314-88G>A		intron	N/A	NP_003801.1
	TNFSF10	NM_001190942.2		c.271-2490G>A		intron	N/A	NP_001177871.1
	TNFSF10	NR_033994.2		n.317-88G>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.314-88G>A		intron	N/A	ENSP00000241261.2
	TNFSF10	ENST00000420541.6	TSL:1	c.271-2490G>A		intron	N/A	ENSP00000389931.2
	TNFSF10	ENST00000430881.1	TSL:5	n.196-88G>A		intron	N/A	ENSP00000404008.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105812 AN: 151960 Hom.: 37221 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.709

GnomAD4 exome AF: 0.681 AC: 555216 AN: 815888 Hom.: 189400 AF XY: 0.680 AC XY: 283132 AN XY: 416404

African (AFR) AF: 0.785 AC: 15293 AN: 19486

American (AMR) AF: 0.502 AC: 11093 AN: 22114

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 13006 AN: 17604

East Asian (EAS) AF: 0.661 AC: 22465 AN: 33968

South Asian (SAS) AF: 0.644 AC: 33698 AN: 52338

European-Finnish (FIN) AF: 0.716 AC: 30306 AN: 42346

Middle Eastern (MID) AF: 0.771 AC: 3197 AN: 4148

European-Non Finnish (NFE) AF: 0.682 AC: 399935 AN: 586224

Other (OTH) AF: 0.696 AC: 26223 AN: 37660

GnomAD4 genome AF: 0.696 AC: 105877 AN: 152078 Hom.: 37239 Cov.: 32 AF XY: 0.694 AC XY: 51580 AN XY: 74358

African (AFR) AF: 0.776 AC: 32189 AN: 41498

American (AMR) AF: 0.569 AC: 8675 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2517 AN: 3466

East Asian (EAS) AF: 0.681 AC: 3520 AN: 5170

South Asian (SAS) AF: 0.634 AC: 3058 AN: 4820

European-Finnish (FIN) AF: 0.704 AC: 7440 AN: 10566

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

European-Non Finnish (NFE) AF: 0.677 AC: 46037 AN: 67980

Other (OTH) AF: 0.706 AC: 1493 AN: 2116

Alfa AF: 0.681 Hom.: 59017

Bravo AF: 0.688

Asia WGS AF: 0.667 AC: 2319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		-0.59
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: rs3815496; hg19: chr3-172227199; COSMIC: COSV53843078; COSMIC: COSV53843078;