rs1757108

Variant names:

• chr9-115083380-C-T
• rs1757108
• NM_002160.4:c.2132-573G>A

Variant summary

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

The NM_002160.4(TNC):​c.2132-573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,824 control chromosomes in the GnomAD database, including 17,502 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 0.47 (17502 hom., cov: 31)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 2 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=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 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.2132-573G>A		intron	N/A	NP_002151.2
	TNC	NM_001439065.1		c.2132-573G>A		intron	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.2132-573G>A		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.2132-573G>A		intron	N/A	ENSP00000265131.4
	TNC	ENST00000423613.6	TSL:1	c.2132-573G>A		intron	N/A	ENSP00000411406.2
	TNC	ENST00000542877.6	TSL:1	c.2132-573G>A		intron	N/A	ENSP00000442242.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71893 AN: 151704 Hom.: 17465 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.474 AC: 71994 AN: 151824 Hom.: 17502 Cov.: 31 AF XY: 0.473 AC XY: 35063 AN XY: 74172

African (AFR) AF: 0.570 AC: 23575 AN: 41384

American (AMR) AF: 0.534 AC: 8145 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1891 AN: 3464

East Asian (EAS) AF: 0.278 AC: 1437 AN: 5162

South Asian (SAS) AF: 0.367 AC: 1761 AN: 4800

European-Finnish (FIN) AF: 0.427 AC: 4501 AN: 10534

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29208 AN: 67910

Other (OTH) AF: 0.467 AC: 984 AN: 2106

Alfa AF: 0.456 Hom.: 1985

Bravo AF: 0.487

Asia WGS AF: 0.393 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.55
DANN	Benign	0.66
PhyloP100		-1.4
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: rs1757108; hg19: chr9-117845659;