1-236394112-T-G

Position:

• chr1-236394112-T-G

Variant summary

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

The ENST00000637660.1(EDARADD):​c.-5-15104T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,060 control chromosomes in the GnomAD database, including 47,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.78 (47365 hom., cov: 32)
• Consequence: EDARADD ENST00000637660.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209

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=-0.88).
• BP6: Variant 1-236394112-T-G is Benign according to our data. Variant chr1-236394112-T-G is described in ClinVar as [Benign]. Clinvar id is 1226215.Status of the report is criteria_provided_single_submitter, 1 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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000439430.5	c.-5-15104T>G		intron_variant		3		ENSP00000405815
EDARADD	ENST00000637660.1	c.-5-15104T>G		intron_variant		5		ENSP00000490347

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118657 AN: 151942 Hom.: 47356 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.919

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.781 AC: 118705 AN: 152060 Hom.: 47365 Cov.: 32 AF XY: 0.786 AC XY: 58422 AN XY: 74340

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.786

Alfa AF: 0.833 Hom.: 67830

Bravo AF: 0.775

Asia WGS AF: 0.870 AC: 3023 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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10802533; hg19: chr1-236557412; COSMIC: COSV62061853; COSMIC: COSV62061853;