rs3749108
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_022336.4(EDAR):c.723G>A(p.Glu241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 1,613,166 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0048 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0070 ( 78 hom. )
Consequence
EDAR
NM_022336.4 synonymous
NM_022336.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.341
Genes affected
EDAR (HGNC:2895): (ectodysplasin A receptor) This gene encodes a member of the tumor necrosis factor receptor family. The encoded transmembrane protein is a receptor for the soluble ligand ectodysplasin A, and can activate the nuclear factor-kappaB, JNK, and caspase-independent cell death pathways. It is required for the development of hair, teeth, and other ectodermal derivatives. Mutations in this gene result in autosomal dominant and recessive forms of hypohidrotic ectodermal dysplasia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 2-108910783-C-T is Benign according to our data. Variant chr2-108910783-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 463881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.341 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00476 (724/152108) while in subpopulation SAS AF= 0.0225 (108/4806). AF 95% confidence interval is 0.019. There are 6 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 6 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDAR | NM_022336.4 | c.723G>A | p.Glu241= | synonymous_variant | 8/12 | ENST00000258443.7 | |
EDAR | XM_006712204.2 | c.819G>A | p.Glu273= | synonymous_variant | 7/11 | ||
RANBP2 | XM_047445367.1 | c.8370+137737C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDAR | ENST00000258443.7 | c.723G>A | p.Glu241= | synonymous_variant | 8/12 | 1 | NM_022336.4 | P1 | |
EDAR | ENST00000376651.1 | c.819G>A | p.Glu273= | synonymous_variant | 7/11 | 2 | |||
EDAR | ENST00000409271.5 | c.819G>A | p.Glu273= | synonymous_variant | 8/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00476 AC: 723AN: 151990Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00754 AC: 1894AN: 251210Hom.: 21 AF XY: 0.00794 AC XY: 1078AN XY: 135778
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GnomAD4 exome AF: 0.00703 AC: 10268AN: 1461058Hom.: 78 Cov.: 34 AF XY: 0.00737 AC XY: 5356AN XY: 726802
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hair morphology 1;C3887494:Ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive;C3888065:Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 11, 2022 | - - |
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. - |
Autosomal recessive hypohidrotic ectodermal dysplasia syndrome;C3888065:Ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at