rs3789867

chr9-115113409-A-Cchr9-115113409-A-Gchr9-115113409-A-T

Variant summary

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

The NM_002160.4(TNC):c.-137+4573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,812 control chromosomes in the GnomAD database, including 11,950 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 0.37 (11950 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.-137+4573T>G		intron_variant		ENST00000350763.9
LOC124902255	XR_007061746.1	n.187+1858A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.-137+4573T>G		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.322+25955A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56760 AN: 151694 Hom.: 11947 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.374 AC: 56760 AN: 151812 Hom.: 11950 Cov.: 32 AF XY: 0.376 AC XY: 27930 AN XY: 74190

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.363

Alfa AF: 0.424 Hom.: 7474

Bravo AF: 0.355

Asia WGS AF: 0.492 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.8
Dann	Benign	0.62

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: rs3789867; hg19: chr9-117875688; COSMIC: COSV60782781; COSMIC: COSV60782781;