Variant 1-236395596-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000359362.6(EDARADD):c.-34C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,551,398 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 35 hom. )

Consequence

EDARADD
ENST00000359362.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.72

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-236395596-C-T is Benign according to our data. Variant chr1-236395596-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1223643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00442 (672/152138) while in subpopulation SAS AF= 0.00704 (34/4830). AF 95% confidence interval is 0.00525. There are 3 homozygotes in gnomad4. There are 340 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4 linkuse as main transcript	c.61+1091C>T		intron_variant		ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.4 linkuse as main transcript	c.-34C>T		5_prime_UTR_variant	1/6		NP_542776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9 linkuse as main transcript	c.61+1091C>T		intron_variant		1	NM_145861.4	ENSP00000335076		Q8WWZ3-1

Frequencies

GnomAD3 genomes

AF:

0.00442

AC:

672

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00881

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00572

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00438

AC:

668

AN:

152546

Hom.:

AF XY:

0.00482

AC XY:

398

AN XY:

82598

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.00426

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00453

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.00576

Gnomad OTH exome

AF:

0.00411

GnomAD4 exome

AF:

0.00526

AC:

7367

AN:

1399260

Hom.:

Cov.:

AF XY:

0.00532

AC XY:

3678

AN XY:

691220

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.00326

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00573

Gnomad4 FIN exome

AF:

0.00921

Gnomad4 NFE exome

AF:

0.00550

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.00442

AC:

672

AN:

152138

Hom.:

Cov.:

AF XY:

0.00457

AC XY:

340

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.00572

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00373

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 05, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.36

DANN

Benign

0.93

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