chr9-115078643-A-G

Variant names:

• chr9-115078643-A-G
• rs1330351
• NM_002160.4:c.2405-431T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002160.4(TNC):​c.2405-431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,754 control chromosomes in the GnomAD database, including 15,424 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 0.44 (15424 hom., cov: 31)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.511 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.2405-431T>C		intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.2405-431T>C		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.2405-431T>C		intron	N/A	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.2405-431T>C		intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.2405-431T>C		intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.2405-431T>C		intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66455 AN: 151636 Hom.: 15418 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.438 AC: 66468 AN: 151754 Hom.: 15424 Cov.: 31 AF XY: 0.441 AC XY: 32726 AN XY: 74140

African (AFR) AF: 0.301 AC: 12460 AN: 41374

American (AMR) AF: 0.409 AC: 6226 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1298 AN: 3464

East Asian (EAS) AF: 0.268 AC: 1380 AN: 5146

South Asian (SAS) AF: 0.501 AC: 2399 AN: 4792

European-Finnish (FIN) AF: 0.583 AC: 6120 AN: 10500

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35021 AN: 67926

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.482 Hom.: 28616

Bravo AF: 0.417

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.76
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1330351; hg19: chr9-117840922; COSMIC: COSV60782708; COSMIC: COSV60782708;