9-115021283-AAGAGAGAGAG-AAGAGAGAGAGAG

Variant names:

• chr9-115021283-A-AAG
• rs766737426
• NM_002160.4:c.6496-18_6496-17dupCT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002160.4(TNC):​c.6496-18_6496-17dupCT variant causes a intron change. The variant allele was found at a frequency of 0.00388 in 1,095,144 control chromosomes in the GnomAD database, including 25 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0089 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (2 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00889 (1331/149700) while in subpopulation AFR AF = 0.0289 (1178/40778). AF 95% confidence interval is 0.0275. There are 23 homozygotes in GnomAd4. There are 624 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1331 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.6496-18_6496-17dupCT		intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.7045-18_7045-17dupCT		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.7045-18_7045-17dupCT		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.6496-18_6496-17dupCT		intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.5677-18_5677-17dupCT		intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.5407-18_5407-17dupCT		intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.00888 AC: 1328 AN: 149594 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00240

Gnomad ASJ AF: 0.00754

Gnomad EAS AF: 0.00604

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000535

Gnomad OTH AF: 0.00685

GnomAD2 exomes AF: 0.00408 AC: 747 AN: 182926 AF XY: 0.00345

Gnomad AFR exome AF: 0.0304

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.00561

Gnomad EAS exome AF: 0.00493

Gnomad FIN exome AF: 0.000602

Gnomad NFE exome AF: 0.000983

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00309 AC: 2920 AN: 945444 Hom.: 2 Cov.: 22 AF XY: 0.00302 AC XY: 1420 AN XY: 470866

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

African (AFR) AF: 0.0322 AC: 741 AN: 23010

American (AMR) AF: 0.00405 AC: 113 AN: 27872

Ashkenazi Jewish (ASJ) AF: 0.00808 AC: 135 AN: 16706

East Asian (EAS) AF: 0.0209 AC: 566 AN: 27132

South Asian (SAS) AF: 0.00289 AC: 164 AN: 56662

European-Finnish (FIN) AF: 0.000256 AC: 8 AN: 31266

Middle Eastern (MID) AF: 0.00339 AC: 13 AN: 3832

European-Non Finnish (NFE) AF: 0.00143 AC: 1027 AN: 720094

Other (OTH) AF: 0.00394 AC: 153 AN: 38870

⚠️ 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: 0.00889 AC: 1331 AN: 149700 Hom.: 23 Cov.: 32 AF XY: 0.00854 AC XY: 624 AN XY: 73048

African (AFR) AF: 0.0289 AC: 1178 AN: 40778

American (AMR) AF: 0.00240 AC: 36 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.00754 AC: 26 AN: 3446

East Asian (EAS) AF: 0.00605 AC: 31 AN: 5120

South Asian (SAS) AF: 0.00213 AC: 10 AN: 4696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000535 AC: 36 AN: 67282

Other (OTH) AF: 0.00678 AC: 14 AN: 2066

Alfa AF: 0.00404 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766737426; hg19: chr9-117783562; COSMIC: COSV104412878;