chr3-172509409-C-T

Position:

• chr3-172509409-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFSF10	NM_003810.4	c.314-88G>A		intron_variant		ENST00000241261.7	NP_003801.1
TNFSF10	NM_001190942.2	c.271-2490G>A		intron_variant			NP_001177871.1
TNFSF10	NR_033994.2	n.317-88G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFSF10	ENST00000241261.7	c.314-88G>A		intron_variant		1	NM_003810.4	ENSP00000241261	P1
TNFSF10	ENST00000420541.6	c.271-2490G>A		intron_variant		1		ENSP00000389931
TNFSF10	ENST00000430881.1	c.197-88G>A		intron_variant, NMD_transcript_variant		5		ENSP00000404008
TNFSF10	ENST00000494851.5	n.397-88G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.785

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.739

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.696

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

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.706

Alfa AF: 0.680 Hom.: 46404

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.68

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: rs3815496; hg19: chr3-172227199; COSMIC: COSV53843078; COSMIC: COSV53843078;