Variant chr1-236409175-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4 linkuse as main transcript	c.62-41A>G		intron_variant		ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.4 linkuse as main transcript	c.32-41A>G		intron_variant			NP_542776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9 linkuse as main transcript	c.62-41A>G		intron_variant		1	NM_145861.4	ENSP00000335076		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

GnomAD3 exomes

AF:

0.525

AC:

127524

AN:

242702

Hom.:

34804

AF XY:

0.529

AC XY:

69358

AN XY:

131034

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 SAS exome

AF:

0.491

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

Gnomad4 AFR exome

AF:

0.477

Gnomad4 AMR exome

AF:

0.445

Gnomad4 ASJ exome

AF:

0.528

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.596

Gnomad4 NFE exome

AF:

0.599

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.533

AC:

81006

AN:

151880

Hom.:

22076

Cov.:

AF XY:

0.531

AC XY:

39435

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.522

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.599

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.540

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over