Genetic Variant TNC:c.-137+4573T>G (chr9-115113409-A-C) – 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+4573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,812 control chromosomes in the GnomAD database, including 11,950 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 0.37 ( 11950 hom., cov: 32)

Consequence

TNC
NM_002160.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.488

Publications

3 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNC	NM_002160.4	MANE Select	c.-137+4573T>G	intron	N/A	NP_002151.2
TNC	NM_001439065.1		c.-137+4573T>G	intron	N/A	NP_001425994.1
TNC	NM_001439066.1		c.-137+1594T>G	intron	N/A	NP_001425995.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TNC	ENST00000350763.9	TSL:1 MANE Select	c.-137+4573T>G	intron	N/A	ENSP00000265131.4
TNC	ENST00000542877.6	TSL:1	c.-137+4573T>G	intron	N/A	ENSP00000442242.1
TNC	ENST00000537320.6	TSL:5	c.-137+4573T>G	intron	N/A	ENSP00000443478.1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56760

AN:

151694

Hom.:

11947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.324

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.518

Gnomad FIN

AF:

0.468

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.361

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

GnomAD4 genome

AF:

0.374

AC:

56760

AN:

151812

Hom.:

11950

Cov.:

AF XY:

0.376

AC XY:

27930

AN XY:

74190

show subpopulations

African (AFR)

AF:

0.176

AC:

7309

AN:

41478

American (AMR)

AF:

0.336

AC:

5143

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

1123

AN:

3464

East Asian (EAS)

AF:

0.608

AC:

3114

AN:

5122

South Asian (SAS)

AF:

0.518

AC:

2495

AN:

4816

European-Finnish (FIN)

AF:

0.468

AC:

4924

AN:

10522

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31267

AN:

67814

Other (OTH)

AF:

0.363

AC:

767

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1710

3420

5130

6840

8550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.423

Hom.:

10164

Bravo

AF:

0.355

Asia WGS

AF:

0.492

AC:

1707

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.8

(source)

DANN

Benign

0.62

PhyloP100

0.49

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over