9-115024229-G-A

Position:

• chr9-115024229-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002160.4(TNC):​c.6332-93C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,382,088 control chromosomes in the GnomAD database, including 1,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (321 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1325 hom.)
• Consequence: TNC NM_002160.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.320

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-115024229-G-A is Benign according to our data. Variant chr9-115024229-G-A is described in ClinVar as [Benign]. Clinvar id is 1288564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNC	NM_002160.4	c.6332-93C>T		intron_variant		ENST00000350763.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNC	ENST00000350763.9	c.6332-93C>T		intron_variant		1	NM_002160.4	P1
DELEC1	ENST00000649121.1	n.78+54568G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8822 AN: 152142 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0419 AC: 51548 AN: 1229828 Hom.: 1325 AF XY: 0.0408 AC XY: 24886 AN XY: 610400

Gnomad4 AFR exome AF: 0.0937

Gnomad4 AMR exome AF: 0.0383

Gnomad4 ASJ exome AF: 0.0547

Gnomad4 EAS exome AF: 0.0000526

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.0453

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0580 AC: 8830 AN: 152260 Hom.: 321 Cov.: 32 AF XY: 0.0551 AC XY: 4101 AN XY: 74466

Gnomad4 AFR AF: 0.0994

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0278 Hom.: 24

Bravo AF: 0.0634

Asia WGS AF: 0.0100 AC: 38 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.45

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: rs10982498; hg19: chr9-117786508;