rs2296765

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001399.5(EDA):c.742-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,197,800 control chromosomes in the GnomAD database, including 50,071 homozygotes. There are 131,017 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 3863 hom., 9668 hem., cov: 23)

Exomes 𝑓: 0.35 ( 46208 hom. 121349 hem. )

Consequence

EDA
NM_001399.5 intron

Scores

Splicing: ADA: 0.00005388

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.351

Publications

7 publications found

Variant links:

Genes affected

EDA (HGNC:3157): (ectodysplasin A) The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

EDA Gene-Disease associations (from GenCC):

tooth agenesis, selective, X-linked, 1
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
X-linked hypohidrotic ectodermal dysplasia
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EDA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant X-70030458-C-T is Benign according to our data. Variant chrX-70030458-C-T is described in ClinVar as Benign. ClinVar VariationId is 44207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5 link	c.742-11C>T		intron_variant	Intron 5 of 7	ENST00000374552.9	NP_001390.1	Q92838-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9 link	c.742-11C>T		intron_variant	Intron 5 of 7	1	NM_001399.5	ENSP00000363680.4		Q92838-1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

33144

AN:

110666

Hom.:

3861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.0882

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.336

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.314

GnomAD2 exomes

AF:

0.299

AC:

50482

AN:

168641

AF XY:

0.292

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.0900

Gnomad FIN exome

AF:

0.409

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.346

AC:

375820

AN:

1087078

Hom.:

46208

Cov.:

AF XY:

0.341

AC XY:

121349

AN XY:

355850

show subpopulations

African (AFR)

AF:

0.193

AC:

5069

AN:

26228

American (AMR)

AF:

0.246

AC:

8518

AN:

34627

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

7641

AN:

19288

East Asian (EAS)

AF:

0.0674

AC:

2023

AN:

30008

South Asian (SAS)

AF:

0.251

AC:

13294

AN:

52919

European-Finnish (FIN)

AF:

0.409

AC:

16370

AN:

40064

Middle Eastern (MID)

AF:

0.376

AC:

1545

AN:

4107

European-Non Finnish (NFE)

AF:

0.367

AC:

305948

AN:

834117

Other (OTH)

AF:

0.337

AC:

15412

AN:

45720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

8239

16479

24718

32958

41197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10372

20744

31116

41488

51860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

33156

AN:

110722

Hom.:

3863

Cov.:

AF XY:

0.293

AC XY:

9668

AN XY:

32962

show subpopulations

African (AFR)

AF:

0.193

AC:

5889

AN:

30558

American (AMR)

AF:

0.282

AC:

2947

AN:

10465

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1034

AN:

2640

East Asian (EAS)

AF:

0.0887

AC:

310

AN:

3493

South Asian (SAS)

AF:

0.235

AC:

614

AN:

2616

European-Finnish (FIN)

AF:

0.426

AC:

2492

AN:

5854

Middle Eastern (MID)

AF:

0.332

AC:

AN:

211

European-Non Finnish (NFE)

AF:

0.362

AC:

19078

AN:

52714

Other (OTH)

AF:

0.314

AC:

473

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

831

1663

2494

3326

4157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.343

Hom.:

15980

Bravo

AF:

0.289

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 22, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypohidrotic X-linked ectodermal dysplasia

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000054

dbscSNV1_RF

Benign

0.048

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over