rs955450

Variant names:

• chr9-115070827-G-A
• rs955450
• NM_002160.4:c.3214+2776C>T

Variant summary

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

The NM_002160.4(TNC):​c.3214+2776C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,198 control chromosomes in the GnomAD database, including 47,449 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 0.78 (47449 hom., cov: 33)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.3214+2776C>T		intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.3214+2776C>T		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.3214+2776C>T		intron	N/A	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.3214+2776C>T		intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.3214+2776C>T		intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.3214+2776C>T		intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119282 AN: 152082 Hom.: 47384 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.785 AC: 119406 AN: 152198 Hom.: 47449 Cov.: 33 AF XY: 0.783 AC XY: 58240 AN XY: 74398

African (AFR) AF: 0.917 AC: 38115 AN: 41562

American (AMR) AF: 0.740 AC: 11301 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2551 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2866 AN: 5166

South Asian (SAS) AF: 0.673 AC: 3242 AN: 4814

European-Finnish (FIN) AF: 0.774 AC: 8201 AN: 10594

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50445 AN: 67996

Other (OTH) AF: 0.785 AC: 1658 AN: 2112

Alfa AF: 0.764 Hom.: 11277

Bravo AF: 0.786

Asia WGS AF: 0.647 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.5
DANN	Benign	0.67
PhyloP100		0.035
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: rs955450; hg19: chr9-117833106;