1-236409175-A-G

Variant names:

Variant summary

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

The NM_145861.4(EDARADD):c.62-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,536,620 control chromosomes in the GnomAD database, including 252,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22076 hom., cov: 31)

Exomes 𝑓: 0.57 ( 230087 hom. )

Consequence

EDARADD
NM_145861.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.278

Publications

10 publications found

Variant links:

Genes affected

EDARADD (HGNC:14341): (EDAR associated via death domain) This gene was identified by its association with ectodermal dysplasia, a genetic disorder characterized by defective development of hair, teeth, and eccrine sweat glands. The protein encoded by this gene is a death domain-containing protein, and is found to interact with EDAR, a death domain receptor known to be required for the development of hair, teeth and other ectodermal derivatives. This protein and EDAR are coexpressed in epithelial cells during the formation of hair follicles and teeth. Through its interaction with EDAR, this protein acts as an adaptor, and links the receptor to downstream signaling pathways. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

EDARADD Gene-Disease associations (from GenCC):

ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant
Inheritance: AD, SD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal dominant hypohidrotic ectodermal dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive hypohidrotic ectodermal dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EDARADD 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=-0.85).

BP6

Variant 1-236409175-A-G is Benign according to our data. Variant chr1-236409175-A-G is described in ClinVar as [Benign]. Clinvar id is 1255368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4 link	c.62-41A>G	intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2	Q8WWZ3-1
EDARADD	NM_080738.5 link	c.32-41A>G	intron_variant	Intron 1 of 5		NP_542776.1	Q8WWZ3-2
EDARADD	NM_001422628.1 link	c.-5-41A>G	intron_variant	Intron 3 of 7		NP_001409557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9 link	c.62-41A>G		intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4		Q8WWZ3-1

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80908

AN:

151762

Hom.:

22044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.599

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.525

AC:

127524

AN:

242702

AF XY:

0.529

show subpopulations

Gnomad AFR exome

AF:

0.477

Gnomad AMR exome

AF:

0.437

Gnomad ASJ exome

AF:

0.525

Gnomad EAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.599

Gnomad NFE exome

AF:

0.594

Gnomad OTH exome

AF:

0.551

GnomAD4 exome

AF:

0.570

AC:

789027

AN:

1384740

Hom.:

230087

Cov.:

AF XY:

0.568

AC XY:

393499

AN XY:

692358

show subpopulations

African (AFR)

AF:

0.477

AC:

15089

AN:

31622

American (AMR)

AF:

0.445

AC:

19001

AN:

42698

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

13358

AN:

25298

East Asian (EAS)

AF:

0.205

AC:

8034

AN:

39184

South Asian (SAS)

AF:

0.493

AC:

40095

AN:

81306

European-Finnish (FIN)

AF:

0.596

AC:

31666

AN:

53092

Middle Eastern (MID)

AF:

0.443

AC:

2474

AN:

5580

European-Non Finnish (NFE)

AF:

0.599

AC:

627523

AN:

1048340

Other (OTH)

AF:

0.552

AC:

31787

AN:

57620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

15470

30941

46411

61882

77352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.533

AC:

81006

AN:

151880

Hom.:

22076

Cov.:

AF XY:

0.531

AC XY:

39435

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.480

AC:

19869

AN:

41416

American (AMR)

AF:

0.489

AC:

7446

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1812

AN:

3470

East Asian (EAS)

AF:

0.263

AC:

1358

AN:

5170

South Asian (SAS)

AF:

0.496

AC:

2386

AN:

4814

European-Finnish (FIN)

AF:

0.599

AC:

6300

AN:

10516

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.590

AC:

40068

AN:

67940

Other (OTH)

AF:

0.540

AC:

1139

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1905

3810

5716

7621

9526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.553

Hom.:

4951

Bravo

AF:

0.518

Asia WGS

AF:

0.420

AC:

1462

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.65

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

1-236409175-A-G

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