1-236394112-T-G

Variant names:

• chr1-236394112-T-G
• rs10802533
• NM_001422628.1:c.-5-15104T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001422628.1(EDARADD):​c.-5-15104T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,060 control chromosomes in the GnomAD database, including 47,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (47365 hom., cov: 32)
• Consequence: EDARADD NM_001422628.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-236394112-T-G is Benign according to our data. Variant chr1-236394112-T-G is described in ClinVar as [Benign]. Clinvar id is 1226215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_001422628.1	c.-5-15104T>G		intron_variant	Intron 3 of 7		NP_001409557.1
EDARADD	NM_145861.4	c.-333T>G		upstream_gene_variant		ENST00000334232.9	NP_665860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000637660.1	c.-5-15104T>G		intron_variant	Intron 1 of 5	5		ENSP00000490347.1
EDARADD	ENST00000439430.5	c.-5-15104T>G		intron_variant	Intron 3 of 7	3		ENSP00000405815.1
EDARADD	ENST00000334232.9	c.-333T>G		upstream_gene_variant		1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118657 AN: 151942 Hom.: 47356 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.790

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118705 AN: 152060 Hom.: 47365 Cov.: 32 AF XY: 0.786 AC XY: 58422 AN XY: 74340

African (AFR) AF: 0.601 AC: 24884 AN: 41416

American (AMR) AF: 0.865 AC: 13211 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2940 AN: 3470

East Asian (EAS) AF: 0.918 AC: 4750 AN: 5172

South Asian (SAS) AF: 0.917 AC: 4420 AN: 4820

European-Finnish (FIN) AF: 0.814 AC: 8611 AN: 10576

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57209 AN: 68014

Other (OTH) AF: 0.786 AC: 1655 AN: 2106

Alfa AF: 0.830 Hom.: 80502

Bravo AF: 0.775

Asia WGS AF: 0.870 AC: 3023 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		-0.21
PromoterAI		0.011	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10802533; hg19: chr1-236557412; COSMIC: COSV62061853; COSMIC: COSV62061853;