9-115078463-G-C

Variant names:

• chr9-115078463-G-C
• rs1330349
• NM_002160.4:c.2405-251C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001439065.1(TNC):​c.2405-251C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 150,400 control chromosomes in the GnomAD database, including 20,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (20954 hom., cov: 27)
• Consequence: TNC NM_001439065.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-115078463-G-C is Benign according to our data. Variant chr9-115078463-G-C is described in ClinVar as Benign. ClinVar VariationId is 1280678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439065.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.2405-251C>G		intron	N/A	NP_002151.2
	TNC	NM_001439065.1		c.2405-251C>G		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.2405-251C>G		intron	N/A	NP_001425995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.2405-251C>G		intron	N/A	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.2405-251C>G		intron	N/A	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.2405-251C>G		intron	N/A	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 78567 AN: 150286 Hom.: 20945 Cov.: 27

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.523 AC: 78602 AN: 150400 Hom.: 20954 Cov.: 27 AF XY: 0.521 AC XY: 38217 AN XY: 73302

African (AFR) AF: 0.478 AC: 19554 AN: 40876

American (AMR) AF: 0.470 AC: 7092 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1516 AN: 3458

East Asian (EAS) AF: 0.267 AC: 1366 AN: 5124

South Asian (SAS) AF: 0.522 AC: 2454 AN: 4700

European-Finnish (FIN) AF: 0.596 AC: 6084 AN: 10210

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.572 AC: 38695 AN: 67646

Other (OTH) AF: 0.472 AC: 985 AN: 2088

Alfa AF: 0.549 Hom.: 2818

Bravo AF: 0.510

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		1.3
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: rs1330349; hg19: chr9-117840742; COSMIC: COSV60789776; COSMIC: COSV60789776;