rs1556220

chr9-115050498-T-C

Variant summary

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

The NM_002160.4(TNC):c.4580-1966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 152,228 control chromosomes in the GnomAD database, including 379 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 0.060 (379 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.4580-1966A>G		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.4580-1966A>G		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-33757T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9087 AN: 152110 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0598 AC: 9109 AN: 152228 Hom.: 379 Cov.: 32 AF XY: 0.0610 AC XY: 4542 AN XY: 74436

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.0966

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0376 Hom.: 226

Bravo AF: 0.0643

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.2
Dann	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1556220; hg19: chr9-117812777;