rs955450

chr9-115070827-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.3214+2776C>T		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.3214+2776C>T		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-13428G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.774

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.785

Alfa AF: 0.761 Hom.: 10955

Bravo AF: 0.786

Asia WGS AF: 0.647 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.5
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs955450; hg19: chr9-117833106;