Genetic Variant ENST00000648852.1:n.277-49619C>T (chr9-115019377-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.528

Publications

11 publications found

Variant links:

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]

DELEC1 links:

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: Labcorp Genetics (formerly Invitae), PanelApp Australia
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

TNC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNC	NM_002160.4 link	c.*1780G>A		downstream_gene_variant		ENST00000350763.9	NP_002151.2	P24821-1Q4LE33B4E1W8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DELEC1	ENST00000648852.1 link	n.277-49619C>T	intron_variant	Intron 3 of 5
DELEC1	ENST00000649121.1 link	n.78+49716C>T	intron_variant	Intron 1 of 6
TNC	ENST00000350763.9 link	c.*1780G>A	downstream_gene_variant		1	NM_002160.4	ENSP00000265131.4	P24821-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61320

AN:

151886

Hom.:

13508

Cov.:

show subpopulations

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.:

AF XY:

0.404

AC XY:

30057

AN XY:

74308

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1782

3564

5346

7128

8910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.4

(source)

DANN

Benign

0.65

PhyloP100

0.53

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over