9-115019377-C-T

Variant names:

• chr9-115019377-C-T
• rs11787664
• ENST00000648852.1:n.277-49619C>T

Variant summary

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

The ENST00000648852.1(DELEC1):​n.277-49619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,004 control chromosomes in the GnomAD database, including 13,508 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 0.40 (13508 hom., cov: 32)
• Consequence: DELEC1 ENST00000648852.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• Publications: 11 publications found

Genes affected

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]

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]

TNC Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 56

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648852.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNC	NM_002160.4	MANE Select	c.*1780G>A		downstream_gene	N/A	NP_002151.2	P24821-1
	TNC	NM_001439065.1		c.*1780G>A		downstream_gene	N/A	NP_001425994.1
	TNC	NM_001439066.1		c.*1780G>A		downstream_gene	N/A	NP_001425995.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DELEC1	ENST00000648852.1		n.277-49619C>T		intron	N/A
	DELEC1	ENST00000649121.1		n.78+49716C>T		intron	N/A
	TNC	ENST00000350763.9	TSL:1 MANE Select	c.*1780G>A		downstream_gene	N/A	ENSP00000265131.4	P24821-1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61320 AN: 151886 Hom.: 13508 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.404 AC: 61336 AN: 152004 Hom.: 13508 Cov.: 32 AF XY: 0.404 AC XY: 30057 AN XY: 74308

African (AFR) AF: 0.241 AC: 10004 AN: 41448

American (AMR) AF: 0.332 AC: 5078 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1180 AN: 3464

East Asian (EAS) AF: 0.345 AC: 1784 AN: 5164

South Asian (SAS) AF: 0.408 AC: 1967 AN: 4826

European-Finnish (FIN) AF: 0.552 AC: 5823 AN: 10548

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34036 AN: 67954

Other (OTH) AF: 0.392 AC: 827 AN: 2110

Alfa AF: 0.436 Hom.: 29412

Bravo AF: 0.379

Asia WGS AF: 0.367 AC: 1278 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.65
PhyloP100		0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11787664;

hg19: chr9-117781656;