9-115021283-AAGAGAGAGAG-AAGAGAGAG

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002160.4(TNC):​c.6496-18_6496-17delCT variant causes a intron change. The variant allele was found at a frequency of 0.012 in 1,040,288 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -2 ACMG points.

• BP6: Variant 9-115021283-AAG-A is Benign according to our data. Variant chr9-115021283-AAG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1316716.Status of the report is criteria_provided_single_submitter, 1 stars.

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_6496-17delCT		intron	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.7045-18_7045-17delCT		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.7045-18_7045-17delCT		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_6496-17delCT		intron	N/A	ENSP00000265131.4	P24821-1
	TNC	ENST00000423613.6	TSL:1	c.5677-18_5677-17delCT		intron	N/A	ENSP00000411406.2	E9PC84
	TNC	ENST00000542877.6	TSL:1	c.5407-18_5407-17delCT		intron	N/A	ENSP00000442242.1	F5H7V9

Frequencies

GnomAD3 genomes AF: 0.000227 AC: 34 AN: 149582 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000369

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000267

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.000198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.000490

GnomAD2 exomes AF: 0.00757 AC: 1384 AN: 182926 AF XY: 0.00768

Gnomad AFR exome AF: 0.00694

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00710

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.00533

Gnomad OTH exome AF: 0.00796

GnomAD4 exome AF: 0.0140 AC: 12424 AN: 890600 Hom.: 0 AF XY: 0.0135 AC XY: 5993 AN XY: 443140

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

African (AFR) AF: 0.0172 AC: 376 AN: 21854

American (AMR) AF: 0.0123 AC: 317 AN: 25824

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 224 AN: 15404

East Asian (EAS) AF: 0.00786 AC: 199 AN: 25302

South Asian (SAS) AF: 0.0133 AC: 697 AN: 52472

European-Finnish (FIN) AF: 0.00907 AC: 266 AN: 29328

Middle Eastern (MID) AF: 0.0123 AC: 45 AN: 3660

European-Non Finnish (NFE) AF: 0.0144 AC: 9815 AN: 680308

Other (OTH) AF: 0.0133 AC: 485 AN: 36448

⚠️ 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: 0.000220 AC: 33 AN: 149688 Hom.: 0 Cov.: 32 AF XY: 0.000205 AC XY: 15 AN XY: 73038

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

African (AFR) AF: 0.000368 AC: 15 AN: 40782

American (AMR) AF: 0.000267 AC: 4 AN: 15006

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

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

European-Finnish (FIN) AF: 0.000198 AC: 2 AN: 10100

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

European-Non Finnish (NFE) AF: 0.000149 AC: 10 AN: 67278

Other (OTH) AF: 0.000484 AC: 1 AN: 2064

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000231617), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0139 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;