9-115042388-T-C

Variant names:

• chr9-115042388-T-C
• rs7021589
• NM_002160.4:c.5126-47A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):​c.5126-47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,604,146 control chromosomes in the GnomAD database, including 15,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1039 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14583 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0510
• Publications: 18 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-115042388-T-C is Benign according to our data. Variant chr9-115042388-T-C is described in ClinVar as Benign. ClinVar VariationId is 1274158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.5126-47A>G		intron_variant	Intron 17 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5126-47A>G		intron_variant	Intron 17 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.0996 AC: 15155 AN: 152186 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.0875

GnomAD2 exomes AF: 0.108 AC: 26324 AN: 244230 AF XY: 0.112

Gnomad AFR exome AF: 0.0243

Gnomad AMR exome AF: 0.0456

Gnomad ASJ exome AF: 0.0516

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.135 AC: 196252 AN: 1451842 Hom.: 14583 Cov.: 31 AF XY: 0.135 AC XY: 97811 AN XY: 721992

African (AFR) AF: 0.0197 AC: 648 AN: 32812

American (AMR) AF: 0.0466 AC: 2006 AN: 43030

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 1366 AN: 25558

East Asian (EAS) AF: 0.000303 AC: 12 AN: 39588

South Asian (SAS) AF: 0.121 AC: 10353 AN: 85356

European-Finnish (FIN) AF: 0.152 AC: 8073 AN: 52976

Middle Eastern (MID) AF: 0.0852 AC: 485 AN: 5694

European-Non Finnish (NFE) AF: 0.150 AC: 166338 AN: 1106986

Other (OTH) AF: 0.116 AC: 6971 AN: 59842

GnomAD4 genome AF: 0.0995 AC: 15156 AN: 152304 Hom.: 1039 Cov.: 32 AF XY: 0.0983 AC XY: 7324 AN XY: 74476

African (AFR) AF: 0.0244 AC: 1016 AN: 41588

American (AMR) AF: 0.0727 AC: 1111 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 217 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.110 AC: 530 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1550 AN: 10616

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10267 AN: 68010

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.121 Hom.: 517

Bravo AF: 0.0882

Asia WGS AF: 0.0480 AC: 166 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.78
PhyloP100		0.051
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7021589; hg19: chr9-117804667; COSMIC: COSV60792675; COSMIC: COSV60792675;