Genetic Variant NM_002160.4:c.-137+112T>C (chr9-115117870-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002160.4(TNC):c.-137+112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,026 control chromosomes in the GnomAD database, including 6,190 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6190 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

TNC
NM_002160.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.45

Publications

7 publications found

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:

LOC124902255 (HGNC:):

LOC124902255 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.-137+112T>C		intron_variant	Intron 1 of 27	ENST00000350763.9	NP_002151.2	P24821-1Q4LE33B4E1W8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9 link	c.-137+112T>C		intron_variant	Intron 1 of 27	1	NM_002160.4	ENSP00000265131.4		P24821-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42575

AN:

151906

Hom.:

6183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.280

AC:

42579

AN:

152024

Hom.:

6190

Cov.:

AF XY:

0.280

AC XY:

20794

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.220

AC:

9119

AN:

41442

American (AMR)

AF:

0.273

AC:

4169

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1323

AN:

3472

East Asian (EAS)

AF:

0.190

AC:

979

AN:

5162

South Asian (SAS)

AF:

0.378

AC:

1822

AN:

4818

European-Finnish (FIN)

AF:

0.257

AC:

2723

AN:

10578

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21328

AN:

67958

Other (OTH)

AF:

0.278

AC:

587

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1603

3206

4808

6411

8014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.179

Hom.:

370

Bravo

AF:

0.275

Asia WGS

AF:

0.312

AC:

1086

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.020

(source)

DANN

Benign

0.35

PhyloP100

-5.4

PromoterAI

-0.0074

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over