1-236394628-G-A

Position:

• chr1-236394628-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145861.4(EDARADD):​c.61+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 720,314 control chromosomes in the GnomAD database, including 245,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (45731 hom., cov: 32)
  • Exomes 𝑓: 0.83 (199289 hom.)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.373

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-236394628-G-A is Benign according to our data. Variant chr1-236394628-G-A is described in ClinVar as [Benign]. Clinvar id is 439637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.61+123G>A		intron_variant		ENST00000334232.9	NP_665860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.61+123G>A		intron_variant		1	NM_145861.4	ENSP00000335076
EDARADD	ENST00000439430.5	c.-5-14588G>A		intron_variant		3		ENSP00000405815
EDARADD	ENST00000637660.1	c.-5-14588G>A		intron_variant		5		ENSP00000490347

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115893 AN: 152040 Hom.: 45725 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.776

GnomAD4 exome AF: 0.834 AC: 473767 AN: 568156 Hom.: 199289 AF XY: 0.838 AC XY: 243430 AN XY: 290574

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.844

Gnomad4 EAS exome AF: 0.949

Gnomad4 SAS exome AF: 0.903

Gnomad4 FIN exome AF: 0.814

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.819

GnomAD4 genome AF: 0.762 AC: 115935 AN: 152158 Hom.: 45731 Cov.: 32 AF XY: 0.767 AC XY: 57096 AN XY: 74394

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.919

Gnomad4 SAS AF: 0.916

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.771

Alfa AF: 0.831 Hom.: 58517

Bravo AF: 0.754

Asia WGS AF: 0.860 AC: 2989 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.61

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: rs966364; hg19: chr1-236557928;