9-115093228-G-C

Variant names:

• chr9-115093228-G-C
• rs1272041
• NM_002160.4:c.-136-2074C>G

Variant summary

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

The NM_002160.4(TNC):​c.-136-2074C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,858 control chromosomes in the GnomAD database, including 13,819 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 0.42 (13819 hom., cov: 31)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 4 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]

LOC124902255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.-136-2074C>G		intron_variant	Intron 1 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.-136-2074C>G		intron_variant	Intron 1 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63890 AN: 151738 Hom.: 13776 Cov.: 31

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.421 AC: 63991 AN: 151858 Hom.: 13819 Cov.: 31 AF XY: 0.423 AC XY: 31364 AN XY: 74216

African (AFR) AF: 0.507 AC: 20990 AN: 41380

American (AMR) AF: 0.482 AC: 7359 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1676 AN: 3464

East Asian (EAS) AF: 0.285 AC: 1470 AN: 5152

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4820

European-Finnish (FIN) AF: 0.409 AC: 4310 AN: 10536

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25195 AN: 67930

Other (OTH) AF: 0.418 AC: 881 AN: 2106

Alfa AF: 0.233 Hom.: 472

Bravo AF: 0.430

Asia WGS AF: 0.384 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.7
DANN	Benign	0.26
PhyloP100		0.49
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: rs1272041; hg19: chr9-117855507;