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rs2992147

chr9-115087035-T-Cchr9-115087035-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002160.4(TNC):c.696A>G(p.Val232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,613,822 control chromosomes in the GnomAD database, including 158,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17667 hom., cov: 34)
Exomes 𝑓: 0.44 ( 140852 hom. )

Consequence

TNC
NM_002160.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.850
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-115087035-T-C is Benign according to our data. Variant chr9-115087035-T-C is described in ClinVar as [Benign]. Clinvar id is 1280191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-115087035-T-C is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.85 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNCNM_002160.4 linkuse as main transcriptc.696A>G p.Val232= synonymous_variant 3/28 ENST00000350763.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNCENST00000350763.9 linkuse as main transcriptc.696A>G p.Val232= synonymous_variant 3/281 NM_002160.4 P1P24821-1
DELEC1ENST00000649121.1 linkuse as main transcriptn.208-305T>C intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.476
AC:
72248
AN:
151882
Hom.:
17625
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.573
Gnomad AMI
AF:
0.383
Gnomad AMR
AF:
0.535
Gnomad ASJ
AF:
0.547
Gnomad EAS
AF:
0.280
Gnomad SAS
AF:
0.368
Gnomad FIN
AF:
0.427
Gnomad MID
AF:
0.503
Gnomad NFE
AF:
0.431
Gnomad OTH
AF:
0.468
GnomAD3 exomes
AF:
0.447
AC:
112281
AN:
251240
Hom.:
26041
AF XY:
0.440
AC XY:
59792
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.578
Gnomad AMR exome
AF:
0.572
Gnomad ASJ exome
AF:
0.556
Gnomad EAS exome
AF:
0.254
Gnomad SAS exome
AF:
0.383
Gnomad FIN exome
AF:
0.434
Gnomad NFE exome
AF:
0.431
Gnomad OTH exome
AF:
0.458
GnomAD4 exome
AF:
0.436
AC:
637220
AN:
1461822
Hom.:
140852
Cov.:
84
AF XY:
0.434
AC XY:
315259
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.584
Gnomad4 AMR exome
AF:
0.573
Gnomad4 ASJ exome
AF:
0.549
Gnomad4 EAS exome
AF:
0.293
Gnomad4 SAS exome
AF:
0.386
Gnomad4 FIN exome
AF:
0.438
Gnomad4 NFE exome
AF:
0.432
Gnomad4 OTH exome
AF:
0.441
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.476
AC:
72354
AN:
152000
Hom.:
17667
Cov.:
34
AF XY:
0.474
AC XY:
35264
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.574
Gnomad4 AMR
AF:
0.536
Gnomad4 ASJ
AF:
0.547
Gnomad4 EAS
AF:
0.280
Gnomad4 SAS
AF:
0.368
Gnomad4 FIN
AF:
0.427
Gnomad4 NFE
AF:
0.431
Gnomad4 OTH
AF:
0.469
Alfa
AF:
0.459
Hom.:
8881
Bravo
AF:
0.488
Asia WGS
AF:
0.395
AC:
1377
AN:
3478
EpiCase
AF:
0.437
EpiControl
AF:
0.444

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 56 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
6.3
Dann
Benign
0.34

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.

Other links and lift over

dbSNP: rs2992147; hg19: chr9-117849314; COSMIC: COSV60782318; COSMIC: COSV60782318; API