rs1757108

Positions:

• chr9-115083380-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002160.4(TNC):​c.2132-573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,824 control chromosomes in the GnomAD database, including 17,502 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 0.47 (17502 hom., cov: 31)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.2132-573G>A		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.2132-573G>A		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-875C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71893 AN: 151704 Hom.: 17465 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.474 AC: 71994 AN: 151824 Hom.: 17502 Cov.: 31 AF XY: 0.473 AC XY: 35063 AN XY: 74172

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.467

Alfa AF: 0.456 Hom.: 1985

Bravo AF: 0.487

Asia WGS AF: 0.393 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.55
DANN	Benign	0.66

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: rs1757108; hg19: chr9-117845659;