3-172523209-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003810.4(TNFSF10):c.132+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,533,212 control chromosomes in the GnomAD database, including 31,150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2993 hom., cov: 33)
  • Exomes 𝑓: 0.19 (28157 hom.)
• Consequence: TNFSF10 NM_003810.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-172523209-T-G is Benign according to our data. Variant chr3-172523209-T-G is described in ClinVar as [Benign]. Clinvar id is 1288782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFSF10	NM_003810.4	c.132+44A>C		intron_variant		ENST00000241261.7
TNFSF10	NM_001190942.2	c.132+44A>C		intron_variant
TNFSF10	NM_001190943.2	c.132+44A>C		intron_variant
TNFSF10	NR_033994.2	n.178+44A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFSF10	ENST00000241261.7	c.132+44A>C		intron_variant		1	NM_003810.4	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27174 AN: 152040 Hom.: 2994 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.218 AC: 51462 AN: 235886 Hom.: 7154 AF XY: 0.222 AC XY: 28313 AN XY: 127814

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.546

Gnomad SAS exome AF: 0.322

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.188 AC: 259782 AN: 1381054 Hom.: 28157 Cov.: 30 AF XY: 0.191 AC XY: 130081 AN XY: 680070

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.513

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.179 AC: 27192 AN: 152158 Hom.: 2993 Cov.: 33 AF XY: 0.185 AC XY: 13759 AN XY: 74392

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.177

Alfa AF: 0.171 Hom.: 5261

Bravo AF: 0.170

Asia WGS AF: 0.441 AC: 1527 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.8
Dann	Benign	0.27

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: rs2270418; hg19: chr3-172240999; COSMIC: COSV53843433; COSMIC: COSV53843433;