chr9-115050512-A-G

Variant names:

• chr9-115050512-A-G
• rs11789200
• NM_002160.4:c.4580-1980T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002160.4(TNC):​c.4580-1980T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,202 control chromosomes in the GnomAD database, including 1,407 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 0.13 (1407 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.4580-1980T>C		intron	N/A	NP_002151.2
	TNC	NM_001439065.1		c.5129-1980T>C		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.5129-1980T>C		intron	N/A	NP_001425995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.4580-1980T>C		intron	N/A	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.4307-8171T>C		intron	N/A	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.3763+2228T>C		intron	N/A	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19074 AN: 152082 Hom.: 1406 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.125 AC: 19079 AN: 152202 Hom.: 1407 Cov.: 32 AF XY: 0.123 AC XY: 9147 AN XY: 74412

African (AFR) AF: 0.0663 AC: 2755 AN: 41524

American (AMR) AF: 0.0770 AC: 1177 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3468

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5186

South Asian (SAS) AF: 0.0827 AC: 399 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2011 AN: 10598

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11949 AN: 67986

Other (OTH) AF: 0.103 AC: 217 AN: 2116

Alfa AF: 0.151 Hom.: 3378

Bravo AF: 0.113

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.67
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs11789200; hg19: chr9-117812791;