rs72758637

Variant names:

• chr9-115042922-C-G
• rs72758637
• NM_002160.4:c.5126-581G>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.5126-581G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,138 control chromosomes in the GnomAD database, including 1,569 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 0.14 (1569 hom., cov: 32)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 11 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4	c.5126-581G>C		intron_variant	Intron 17 of 27	ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.5126-581G>C		intron_variant	Intron 17 of 27	1	NM_002160.4	ENSP00000265131.4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20926 AN: 152020 Hom.: 1567 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.0628

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.138 AC: 20937 AN: 152138 Hom.: 1569 Cov.: 32 AF XY: 0.135 AC XY: 10064 AN XY: 74376

African (AFR) AF: 0.134 AC: 5562 AN: 41496

American (AMR) AF: 0.0871 AC: 1332 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.0628 AC: 325 AN: 5176

South Asian (SAS) AF: 0.117 AC: 564 AN: 4824

European-Finnish (FIN) AF: 0.148 AC: 1571 AN: 10584

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10813 AN: 67974

Other (OTH) AF: 0.116 AC: 246 AN: 2116

Alfa AF: 0.157 Hom.: 249

Bravo AF: 0.130

Asia WGS AF: 0.101 AC: 349 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.25
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: rs72758637; hg19: chr9-117805201;