1-236409068-T-TA

Position:

• chr1-236409068-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000334232.9(EDARADD):​c.62-129dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 332,858 control chromosomes in the GnomAD database, including 768 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (757 hom., cov: 28)
  • Exomes 𝑓: 0.048 (11 hom.)
• Consequence: EDARADD ENST00000334232.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 1-236409068-T-TA is Benign according to our data. Variant chr1-236409068-T-TA is described in ClinVar as [Benign]. Clinvar id is 1255321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-129dup		intron_variant		ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.4	c.32-129dup		intron_variant			NP_542776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.62-129dup		intron_variant		1	NM_145861.4	ENSP00000335076

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 8919 AN: 129002 Hom.: 756 Cov.: 28

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0335

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0258

Gnomad EAS AF: 0.0384

Gnomad SAS AF: 0.00862

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0585

GnomAD4 exome AF: 0.0483 AC: 9854 AN: 203858 Hom.: 11 AF XY: 0.0492 AC XY: 5265 AN XY: 107028

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0539

Gnomad4 ASJ exome AF: 0.0462

Gnomad4 EAS exome AF: 0.0519

Gnomad4 SAS exome AF: 0.0517

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0463

Gnomad4 OTH exome AF: 0.0567

GnomAD4 genome AF: 0.0692 AC: 8930 AN: 129000 Hom.: 757 Cov.: 28 AF XY: 0.0672 AC XY: 4145 AN XY: 61722

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0258

Gnomad4 EAS AF: 0.0387

Gnomad4 SAS AF: 0.00892

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 21, 2021

- -

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;