1-236409068-TAAAAAA-TAAAA

Variant names:

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

Variant summary

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

The NM_145861.4(EDARADD):​c.62-130_62-129delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 326,150 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., cov: 28)
  • Exomes 𝑓: 0.055 (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: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-130_62-129delAA		intron_variant	Intron 1 of 5	ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.5	c.32-130_32-129delAA		intron_variant	Intron 1 of 5		NP_542776.1
EDARADD	NM_001422628.1	c.-5-130_-5-129delAA		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.62-147_62-146delAA		intron_variant	Intron 1 of 5	1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.000124 AC: 16 AN: 129046 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000883

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000116

Gnomad OTH AF: 0.000566

GnomAD4 exome AF: 0.0551 AC: 10867 AN: 197106 Hom.: 0 AF XY: 0.0552 AC XY: 5712 AN XY: 103422

Gnomad4 AFR exome AF: 0.0430

Gnomad4 AMR exome AF: 0.0671

Gnomad4 ASJ exome AF: 0.0600

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.0658

Gnomad4 FIN exome AF: 0.0407

Gnomad4 NFE exome AF: 0.0554

Gnomad4 OTH exome AF: 0.0524

GnomAD4 genome AF: 0.000124 AC: 16 AN: 129044 Hom.: 1 Cov.: 28 AF XY: 0.000146 AC XY: 9 AN XY: 61746

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000159

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000883

Gnomad4 NFE AF: 0.000116

Gnomad4 OTH AF: 0.000564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;