rs944225

Variant names:

• chr9-115061622-T-C
• rs944225
• NM_002160.4:c.4033+1295A>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.4033+1295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,110 control chromosomes in the GnomAD database, including 3,827 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 0.22 (3827 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.4033+1295A>G		intron_variant	Intron 13 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.4033+1295A>G		intron_variant	Intron 13 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33911 AN: 151992 Hom.: 3823 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.223 AC: 33929 AN: 152110 Hom.: 3827 Cov.: 32 AF XY: 0.223 AC XY: 16601 AN XY: 74376

African (AFR) AF: 0.224 AC: 9312 AN: 41498

American (AMR) AF: 0.147 AC: 2241 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3466

East Asian (EAS) AF: 0.186 AC: 963 AN: 5174

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2530 AN: 10576

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16256 AN: 67972

Other (OTH) AF: 0.200 AC: 423 AN: 2112

Alfa AF: 0.243 Hom.: 583

Bravo AF: 0.212

Asia WGS AF: 0.220 AC: 769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		-0.10
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: rs944225; hg19: chr9-117823901;