rs2236409

chr9-115059467-A-Cchr9-115059467-A-Gchr9-115059467-A-T

Variant summary

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

The NM_002160.4(TNC):c.4306+263T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,256 control chromosomes in the GnomAD database, including 476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.073 (476 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.530

Genes affected

TNC (HGNC:5318): (tenascin C) This gene encodes an extracellular matrix protein with a spatially and temporally restricted tissue distribution. This protein is homohexameric with disulfide-linked subunits, and contains multiple EGF-like and fibronectin type-III domains. It is implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity, and neuronal regeneration. [provided by RefSeq, Jul 2011]

DELEC1 (HGNC:23658): (deleted in esophageal cancer 1) The function of this gene is not known. This gene is located in a region commonly deleted in esophageal squamous cell carcinomas. Gene expression is reduced or absent in these carcinomas and thus this is a candidate tumor suppressor gene for esophageal squamous cell carcinomas. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 9-115059467-A-C is Benign according to our data. Variant chr9-115059467-A-C is described in ClinVar as [Benign]. Clinvar id is 1232370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.4306+263T>G		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.4306+263T>G		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-24788A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11058 AN: 152138 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0726 AC: 11053 AN: 152256 Hom.: 476 Cov.: 32 AF XY: 0.0754 AC XY: 5612 AN XY: 74448

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0920

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0741 Hom.: 293

Bravo AF: 0.0676

Asia WGS AF: 0.115 AC: 405 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

Dec 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	8.7
Dann	Benign	0.86

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: rs2236409; hg19: chr9-117821746;