rs139833680

Variant names:

• chr1-236408953-T-G
• rs139833680
• NM_145861.4:c.62-263T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-236408953-T-G
• chr1-236408953-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145861.4(EDARADD):​c.62-263T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 151,486 control chromosomes in the GnomAD database, including 415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.041 (415 hom., cov: 30)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950
• Publications: 0 publications found

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]

EDARADD Gene-Disease associations (from GenCC):

• ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant

  Inheritance: SD, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant hypohidrotic ectodermal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive hypohidrotic ectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-236408953-T-G is Benign according to our data. Variant chr1-236408953-T-G is described in ClinVar as Benign. ClinVar VariationId is 1240648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145861.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDARADD	NM_145861.4	MANE Select	c.62-263T>G		intron	N/A	NP_665860.2	Q8WWZ3-1
	EDARADD	NM_080738.5		c.32-263T>G		intron	N/A	NP_542776.1	Q8WWZ3-2
	EDARADD	NM_001422628.1		c.-5-263T>G		intron	N/A	NP_001409557.1	A0A1B0GV26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDARADD	ENST00000334232.9	TSL:1 MANE Select	c.62-263T>G		intron	N/A	ENSP00000335076.4	Q8WWZ3-1
	EDARADD	ENST00000359362.6	TSL:1	c.32-263T>G		intron	N/A	ENSP00000352320.4	Q8WWZ3-2
	EDARADD	ENST00000637660.1	TSL:5	c.-5-263T>G		intron	N/A	ENSP00000490347.1	A0A1B0GV26

Frequencies

GnomAD3 genomes AF: 0.0408 AC: 6176 AN: 151368 Hom.: 414 Cov.: 30

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00102

Gnomad OTH AF: 0.0270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0409 AC: 6194 AN: 151486 Hom.: 415 Cov.: 30 AF XY: 0.0392 AC XY: 2899 AN XY: 74036

African (AFR) AF: 0.141 AC: 5807 AN: 41236

American (AMR) AF: 0.0156 AC: 237 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00195 AC: 10 AN: 5126

South Asian (SAS) AF: 0.00146 AC: 7 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10478

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00102 AC: 69 AN: 67884

Other (OTH) AF: 0.0267 AC: 56 AN: 2094

Alfa AF: 0.0285 Hom.: 23

Bravo AF: 0.0474

Asia WGS AF: 0.0130 AC: 45 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs139833680; hg19: chr1-236572253;