Variant rs2274751 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002160.4(TNC):c.5512+123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,358,710 control chromosomes in the GnomAD database, including 7,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 688 hom., cov: 33)

Exomes 𝑓: 0.099 ( 6380 hom. )

Consequence

TNC
NM_002160.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.384

Variant links:

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]

TNC links:

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]

DELEC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-115038138-T-A is Benign according to our data. Variant chr9-115038138-T-A is described in ClinVar as [Benign]. Clinvar id is 1274867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNC	NM_002160.4 linkuse as main transcript	c.5512+123A>T		intron_variant		ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9 linkuse as main transcript	c.5512+123A>T		intron_variant		1	NM_002160.4	ENSP00000265131	P1	P24821-1
DELEC1	ENST00000649121.1 linkuse as main transcript	n.79-46117T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0906

AC:

13785

AN:

152160

Hom.:

688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0635

Gnomad SAS

AF:

0.0479

Gnomad FIN

AF:

0.0813

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.121

GnomAD4 exome

AF:

0.0985

AC:

118872

AN:

1206432

Hom.:

6380

AF XY:

0.0983

AC XY:

58267

AN XY:

592770

show subpopulations

Gnomad4 AFR exome

AF:

0.0554

Gnomad4 AMR exome

AF:

0.0864

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.0843

Gnomad4 SAS exome

AF:

0.0523

Gnomad4 FIN exome

AF:

0.0821

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0958

GnomAD4 genome

AF:

0.0905

AC:

13786

AN:

152278

Hom.:

688

Cov.:

AF XY:

0.0892

AC XY:

6640

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0589

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.0635

Gnomad4 SAS

AF:

0.0480

Gnomad4 FIN

AF:

0.0813

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0897

Hom.:

Bravo

AF:

0.0947

Asia WGS

AF:

0.0540

AC:

189

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.4

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over