Genetic Variant EDARADD:c.61+123G>C (chr1-236394628-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145861.4(EDARADD):c.61+123G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EDARADD
NM_145861.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.373

Publications

7 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4 link	c.61+123G>C		intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2	Q8WWZ3-1
EDARADD	NM_001422628.1 link	c.-5-14588G>C		intron_variant	Intron 3 of 7		NP_001409557.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EDARADD	ENST00000334232.9 link	c.61+123G>C	intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4	Q8WWZ3-1
EDARADD	ENST00000637660.1 link	c.-5-14588G>C	intron_variant	Intron 1 of 5	5		ENSP00000490347.1	A0A1B0GV26
EDARADD	ENST00000439430.5 link	c.-5-14588G>C	intron_variant	Intron 3 of 7	3		ENSP00000405815.1	B1AL55

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152078

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

569490

Hom.:

AF XY:

0.00

AC XY:

AN XY:

291204

African (AFR)

AF:

0.00

AC:

AN:

15038

American (AMR)

AF:

0.00

AC:

AN:

15978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13308

East Asian (EAS)

AF:

0.00

AC:

AN:

30430

South Asian (SAS)

AF:

0.00

AC:

AN:

32234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3412

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

390362

Other (OTH)

AF:

0.00

AC:

AN:

28652

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74288

African (AFR)

AF:

0.00

AC:

AN:

41358

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2090

Alfa

AF:

0.00

Hom.:

72076

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.7

(source)

DANN

Benign

0.37

PhyloP100

0.37

PromoterAI

0.021

Neutral

(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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over