rs604070
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_145861.4(EDARADD):c.369C>T(p.Asp123=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,613,874 control chromosomes in the GnomAD database, including 44,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.18 ( 3125 hom., cov: 31)
Exomes 𝑓: 0.23 ( 41725 hom. )
Consequence
EDARADD
NM_145861.4 synonymous
NM_145861.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.198
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 1-236482370-C-T is Benign according to our data. Variant chr1-236482370-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-236482370-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.198 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDARADD | NM_145861.4 | c.369C>T | p.Asp123= | synonymous_variant | 6/6 | ENST00000334232.9 | |
EDARADD | NM_080738.4 | c.339C>T | p.Asp113= | synonymous_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDARADD | ENST00000334232.9 | c.369C>T | p.Asp123= | synonymous_variant | 6/6 | 1 | NM_145861.4 | ||
EDARADD | ENST00000359362.6 | c.339C>T | p.Asp113= | synonymous_variant | 6/6 | 1 | P1 | ||
EDARADD | ENST00000637660.1 | c.303C>T | p.Asp101= | synonymous_variant | 6/6 | 5 | |||
EDARADD | ENST00000642595.1 | c.236-9367C>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.185 AC: 28067AN: 151922Hom.: 3128 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
28067
AN:
151922
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.200 AC: 50249AN: 251446Hom.: 5835 AF XY: 0.205 AC XY: 27892AN XY: 135888
GnomAD3 exomes
AF:
AC:
50249
AN:
251446
Hom.:
AF XY:
AC XY:
27892
AN XY:
135888
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.233 AC: 340197AN: 1461834Hom.: 41725 Cov.: 35 AF XY: 0.232 AC XY: 168488AN XY: 727220
GnomAD4 exome
AF:
AC:
340197
AN:
1461834
Hom.:
Cov.:
35
AF XY:
AC XY:
168488
AN XY:
727220
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.185 AC: 28059AN: 152040Hom.: 3125 Cov.: 31 AF XY: 0.183 AC XY: 13563AN XY: 74302
GnomAD4 genome
?
AF:
AC:
28059
AN:
152040
Hom.:
Cov.:
31
AF XY:
AC XY:
13563
AN XY:
74302
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
420
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 11, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Hypohidrotic Ectodermal Dysplasia, Recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive;C3541517:Ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hypohidrotic ectodermal dysplasia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at