9-115021283-AAGAG-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.6496-20_6496-17delCTCT		intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.7045-20_7045-17delCTCT		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.7045-20_7045-17delCTCT		intron	N/A	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.6496-20_6496-17delCTCT		intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.5677-20_5677-17delCTCT		intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.5407-20_5407-17delCTCT		intron	N/A	ENSP00000442242.1	F5H7V9

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

GnomAD2 exomes AF: 0.000815 AC: 149 AN: 182926 AF XY: 0.000604

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00724 AC: 169 AN: 23330

American (AMR) AF: 0.00103 AC: 29 AN: 28036

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 2 AN: 16838

East Asian (EAS) AF: 0.000256 AC: 7 AN: 27348

South Asian (SAS) AF: 0.000631 AC: 36 AN: 57094

European-Finnish (FIN) AF: 0.0000319 AC: 1 AN: 31382

Middle Eastern (MID) AF: 0.000520 AC: 2 AN: 3848

European-Non Finnish (NFE) AF: 0.000317 AC: 230 AN: 724476

Other (OTH) AF: 0.000767 AC: 30 AN: 39116

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00728 AC: 297 AN: 40786

American (AMR) AF: 0.00120 AC: 18 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000390 AC: 2 AN: 5122

South Asian (SAS) AF: 0.000213 AC: 1 AN: 4696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10114

Middle Eastern (MID) AF: 0.00694 AC: 2 AN: 288

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67292

Other (OTH) AF: 0.000968 AC: 2 AN: 2066

Alfa AF: 0.000221 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs766737426; hg19: chr9-117783562;