rs2274751

chr9-115038138-T-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002160.4(TNC):c.5512+123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,358,710 control chromosomes in the GnomAD database, including 7,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (688 hom., cov: 33)
  • Exomes 𝑓: 0.099 (6380 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.384

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-115038138-T-A is Benign according to our data. Variant chr9-115038138-T-A is described in ClinVar as [Benign]. Clinvar id is 1274867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.5512+123A>T		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.5512+123A>T		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.79-46117T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13785 AN: 152160 Hom.: 688 Cov.: 33

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.0635

Gnomad SAS AF: 0.0479

Gnomad FIN AF: 0.0813

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0985 AC: 118872 AN: 1206432 Hom.: 6380 AF XY: 0.0983 AC XY: 58267 AN XY: 592770

Gnomad4 AFR exome AF: 0.0554

Gnomad4 AMR exome AF: 0.0864

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0843

Gnomad4 SAS exome AF: 0.0523

Gnomad4 FIN exome AF: 0.0821

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0958

GnomAD4 genome AF: 0.0905 AC: 13786 AN: 152278 Hom.: 688 Cov.: 33 AF XY: 0.0892 AC XY: 6640 AN XY: 74452

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.0635

Gnomad4 SAS AF: 0.0480

Gnomad4 FIN AF: 0.0813

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0897 Hom.: 86

Bravo AF: 0.0947

Asia WGS AF: 0.0540 AC: 189 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.4
Dann	Benign	0.69

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: rs2274751; hg19: chr9-117800417; COSMIC: COSV60792841; COSMIC: COSV60792841;