1-236495379-T-C

Position:

• chr1-236495379-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642595.1(EDARADD):​c.*164+3224T>C variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDARADD	ENST00000642595.1	c.*164+3224T>C		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.268

Alfa AF: 0.271 Hom.: 10712

Bravo AF: 0.268

Asia WGS AF: 0.222 AC: 768 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10489788; hg19: chr1-236658679;