9-115021283-AAGAGAGAG-AAGAG

Variant names:

• chr9-115021283-AAGAG-A
• rs766737426
• NM_002160.4:c.6496-20_6496-17delCTCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002160.4(TNC):​c.6496-20_6496-17delCTCT variant causes a intron change. The variant allele was found at a frequency of 0.000758 in 1,101,196 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0022 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (0 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.6496-20_6496-17delCTCT		intron_variant	Intron 27 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.6496-20_6496-17delCTCT		intron_variant	Intron 27 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 329 AN: 149622 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000390

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.000978

GnomAD3 exomes AF: 0.000815 AC: 149 AN: 182926 Hom.: 0 AF XY: 0.000604 AC XY: 60 AN XY: 99294

Gnomad AFR exome AF: 0.00717

Gnomad AMR exome AF: 0.000913

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000747

Gnomad SAS exome AF: 0.000443

Gnomad FIN exome AF: 0.0000669

Gnomad NFE exome AF: 0.000271

Gnomad OTH exome AF: 0.000468

GnomAD4 exome AF: 0.000532 AC: 506 AN: 951468 Hom.: 0 AF XY: 0.000521 AC XY: 247 AN XY: 473752

Gnomad4 AFR exome AF: 0.00724

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.000119

Gnomad4 EAS exome AF: 0.000256

Gnomad4 SAS exome AF: 0.000631

Gnomad4 FIN exome AF: 0.0000319

Gnomad4 NFE exome AF: 0.000317

Gnomad4 OTH exome AF: 0.000767

GnomAD4 genome AF: 0.00220 AC: 329 AN: 149728 Hom.: 4 Cov.: 32 AF XY: 0.00208 AC XY: 152 AN XY: 73060

Gnomad4 AFR AF: 0.00728

Gnomad4 AMR AF: 0.00120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.000968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs766737426; hg19: chr9-117783562;