1-236409068-TAAAAAA-TAAAAAAAAA

Variant names:

• chr1-236409068-T-TAAA
• rs772223735
• NM_145861.4:c.62-131_62-129dupAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_145861.4(EDARADD):​c.62-131_62-129dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 333,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00033 (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000426 (55/129110) while in subpopulation AFR AF= 0.00129 (45/34912). AF 95% confidence interval is 0.00099. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-131_62-129dupAAA		intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.5	c.32-131_32-129dupAAA		intron_variant	Intron 1 of 5		NP_542776.1
EDARADD	NM_001422628.1	c.-5-131_-5-129dupAAA		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_62-147insAAA		intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.000426 AC: 55 AN: 129112 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000239

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000227

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000147

Gnomad MID AF: 0.00347

Gnomad NFE AF: 0.0000497

Gnomad OTH AF: 0.000566

GnomAD4 exome AF: 0.000333 AC: 68 AN: 204118 Hom.: 0 AF XY: 0.000336 AC XY: 36 AN XY: 107170

Gnomad4 AFR exome AF: 0.00172

Gnomad4 AMR exome AF: 0.000841

Gnomad4 ASJ exome AF: 0.000169

Gnomad4 EAS exome AF: 0.000317

Gnomad4 SAS exome AF: 0.000340

Gnomad4 FIN exome AF: 0.000203

Gnomad4 NFE exome AF: 0.000267

Gnomad4 OTH exome AF: 0.000447

GnomAD4 genome AF: 0.000426 AC: 55 AN: 129110 Hom.: 0 Cov.: 28 AF XY: 0.000405 AC XY: 25 AN XY: 61784

Gnomad4 AFR AF: 0.00129

Gnomad4 AMR AF: 0.000239

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000227

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000147

Gnomad4 NFE AF: 0.0000497

Gnomad4 OTH AF: 0.000564

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;