rs2236409

Variant names:

• chr9-115059467-A-C
• rs2236409
• NM_002160.4:c.4306+263T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-115059467-A-C
• chr9-115059467-A-G
• chr9-115059467-A-T

Variant summary

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

The NM_002160.4(TNC):​c.4306+263T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,256 control chromosomes in the GnomAD database, including 476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.073 (476 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.530
• Publications: 6 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=-0.75).
• BP6: Variant 9-115059467-A-C is Benign according to our data. Variant chr9-115059467-A-C is described in ClinVar as Benign. ClinVar VariationId is 1232370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.4306+263T>G		intron	N/A	NP_002151.2
	TNC	NM_001439065.1		c.4306+263T>G		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.4306+263T>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.4306+263T>G		intron	N/A	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.4306+263T>G		intron	N/A	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.3215-2042T>G		intron	N/A	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11058 AN: 152138 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0920

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0726 AC: 11053 AN: 152256 Hom.: 476 Cov.: 32 AF XY: 0.0754 AC XY: 5612 AN XY: 74448

African (AFR) AF: 0.0468 AC: 1946 AN: 41556

American (AMR) AF: 0.0529 AC: 809 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3472

East Asian (EAS) AF: 0.124 AC: 641 AN: 5160

South Asian (SAS) AF: 0.125 AC: 603 AN: 4824

European-Finnish (FIN) AF: 0.0920 AC: 977 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5410 AN: 68002

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0783 Hom.: 1079

Bravo AF: 0.0676

Asia WGS AF: 0.115 AC: 405 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	-0.75
CADD	Benign	8.7
DANN	Benign	0.86
PhyloP100		0.53
PromoterAI		0.017	Neutral
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: rs2236409; hg19: chr9-117821746;