dbSNP rs10118040: TNC:c.-137+847T>C (chr9-115117135-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+847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,996 control chromosomes in the GnomAD database, including 12,597 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 0.40 ( 12597 hom., cov: 32)

Consequence

TNC
NM_002160.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 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+847T>C	intron	N/A	NP_002151.2
TNC	NM_001439065.1		c.-137+847T>C	intron	N/A	NP_001425994.1
TNC	NM_001439066.1		c.-241+847T>C	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+847T>C	intron	N/A	ENSP00000265131.4
TNC	ENST00000542877.6	TSL:1	c.-137+847T>C	intron	N/A	ENSP00000442242.1
TNC	ENST00000901445.1		c.-137+847T>C	intron	N/A	ENSP00000571504.1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60660

AN:

151878

Hom.:

12582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.435

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.386

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

GnomAD4 genome

AF:

0.399

AC:

60710

AN:

151996

Hom.:

12597

Cov.:

AF XY:

0.399

AC XY:

29635

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.394

AC:

16354

AN:

41466

American (AMR)

AF:

0.320

AC:

4882

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1187

AN:

3470

East Asian (EAS)

AF:

0.696

AC:

3587

AN:

5152

South Asian (SAS)

AF:

0.402

AC:

1934

AN:

4810

European-Finnish (FIN)

AF:

0.424

AC:

4477

AN:

10548

Middle Eastern (MID)

AF:

0.442

AC:

129

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

26954

AN:

67964

Other (OTH)

AF:

0.385

AC:

811

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1873

3746

5619

7492

9365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.390

Hom.:

19778

Bravo

AF:

0.394

Asia WGS

AF:

0.484

AC:

1683

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

0.28

(source)

DANN

Benign

0.70

PhyloP100

-1.8

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