1-236414050-T-C

Position:

• chr1-236414050-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145861.4(EDARADD):​c.121-210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,330 control chromosomes in the GnomAD database, including 350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.043 (350 hom., cov: 33)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-236414050-T-C is Benign according to our data. Variant chr1-236414050-T-C is described in ClinVar as [Benign]. Clinvar id is 1287437.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.121-210T>C		intron_variant		ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.4	c.91-210T>C		intron_variant			NP_542776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.121-210T>C		intron_variant		1	NM_145861.4	ENSP00000335076

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6460 AN: 152212 Hom.: 349 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.00413

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00498

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0426 AC: 6491 AN: 152330 Hom.: 350 Cov.: 33 AF XY: 0.0414 AC XY: 3084 AN XY: 74496

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.0311

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.00498

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0291 Hom.: 32

Bravo AF: 0.0481

Asia WGS AF: 0.0340 AC: 120 AN: 3478

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 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.54

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: rs16833652; hg19: chr1-236577350;