chr9-115050512-A-G

Position:

• chr9-115050512-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNC	NM_002160.4	c.4580-1980T>C		intron_variant		ENST00000350763.9	NP_002151.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNC	ENST00000350763.9	c.4580-1980T>C		intron_variant		1	NM_002160.4	ENSP00000265131	P1
DELEC1	ENST00000649121.1	n.79-33743A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.0804

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.0827

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.103

Alfa AF: 0.157 Hom.: 2480

Bravo AF: 0.113

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs11789200; hg19: chr9-117812791;