ENST00000642595.1:n.*164+3224T>C

Variant names:

• chr1-236495379-T-C
• rs10489788
• ENST00000642595.1:n.*164+3224T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642595.1(EDARADD):​n.*164+3224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,946 control chromosomes in the GnomAD database, including 5,198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5198 hom., cov: 29)
• Consequence: EDARADD ENST00000642595.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642595.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDARADD	ENST00000642595.1		n.*164+3224T>C		intron	N/A	ENSP00000494458.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39607 AN: 151834 Hom.: 5190 Cov.: 29

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.261 AC: 39637 AN: 151946 Hom.: 5198 Cov.: 29 AF XY: 0.258 AC XY: 19162 AN XY: 74260

African (AFR) AF: 0.257 AC: 10627 AN: 41426

American (AMR) AF: 0.277 AC: 4220 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 986 AN: 3462

East Asian (EAS) AF: 0.205 AC: 1059 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1116 AN: 4806

European-Finnish (FIN) AF: 0.220 AC: 2334 AN: 10586

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18543 AN: 67936

Other (OTH) AF: 0.268 AC: 565 AN: 2108

Alfa AF: 0.271 Hom.: 21762

Bravo AF: 0.268

Asia WGS AF: 0.222 AC: 768 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.56
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs10489788; hg19: chr1-236658679;