rs1271449

Variant names:

• chr9-115090243-T-C
• rs1271449
• NM_002160.4:c.457+319A>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.457+319A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,932 control chromosomes in the GnomAD database, including 8,166 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 0.33 (8166 hom., cov: 31)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.457+319A>G		intron_variant	Intron 2 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.457+319A>G		intron_variant	Intron 2 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49475 AN: 151814 Hom.: 8145 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.326 AC: 49548 AN: 151932 Hom.: 8166 Cov.: 31 AF XY: 0.326 AC XY: 24219 AN XY: 74258

African (AFR) AF: 0.334 AC: 13831 AN: 41416

American (AMR) AF: 0.400 AC: 6116 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1479 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1235 AN: 5150

South Asian (SAS) AF: 0.309 AC: 1490 AN: 4818

European-Finnish (FIN) AF: 0.286 AC: 3007 AN: 10510

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21402 AN: 67970

Other (OTH) AF: 0.348 AC: 733 AN: 2108

Alfa AF: 0.324 Hom.: 6136

Bravo AF: 0.333

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.61
PhyloP100		0.63
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: rs1271449; hg19: chr9-117852522;