NM_145861.4:c.62-130_62-129dupAA

Variant names:

• chr1-236409068-T-TAA
• rs772223735
• NM_145861.4:c.62-130_62-129dupAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_145861.4(EDARADD):​c.62-130_62-129dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 332,542 control chromosomes in the GnomAD database, including 113 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.023 (113 hom., cov: 28)
  • Exomes 𝑓: 0.0041 (0 hom.)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-130_62-129dupAA		intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.5	c.32-130_32-129dupAA		intron_variant	Intron 1 of 5		NP_542776.1
EDARADD	NM_001422628.1	c.-5-130_-5-129dupAA		intron_variant	Intron 3 of 7		NP_001409557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.62-148_62-147insAA		intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 2904 AN: 129054 Hom.: 114 Cov.: 28

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000739

Gnomad FIN AF: 0.000147

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.000679

Gnomad OTH AF: 0.0193

GnomAD4 exome AF: 0.00405 AC: 825 AN: 203492 Hom.: 0 AF XY: 0.00406 AC XY: 434 AN XY: 106858

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.00576

Gnomad4 ASJ exome AF: 0.00322

Gnomad4 EAS exome AF: 0.00376

Gnomad4 SAS exome AF: 0.00392

Gnomad4 FIN exome AF: 0.00254

Gnomad4 NFE exome AF: 0.00301

Gnomad4 OTH exome AF: 0.00556

GnomAD4 genome AF: 0.0225 AC: 2907 AN: 129050 Hom.: 113 Cov.: 28 AF XY: 0.0226 AC XY: 1397 AN XY: 61754

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000743

Gnomad4 FIN AF: 0.000147

Gnomad4 NFE AF: 0.000679

Gnomad4 OTH AF: 0.0192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs772223735; hg19: chr1-236572368;