1-236405470-C-T

Position:

• chr1-236405470-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145861.4(EDARADD):​c.62-3746C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,966 control chromosomes in the GnomAD database, including 23,022 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23022 hom., cov: 31)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.62-3746C>T		intron_variant		ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.5	c.32-3746C>T		intron_variant			NP_542776.1
EDARADD	NM_001422628.1	c.-5-3746C>T		intron_variant			NP_001409557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.62-3746C>T		intron_variant		1	NM_145861.4	ENSP00000335076.4

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81350 AN: 151848 Hom.: 23006 Cov.: 31

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.536 AC: 81400 AN: 151966 Hom.: 23022 Cov.: 31 AF XY: 0.533 AC XY: 39575 AN XY: 74272

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.544

Alfa AF: 0.622 Hom.: 37431

Bravo AF: 0.519

Asia WGS AF: 0.400 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.69

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: rs608825; hg19: chr1-236568770;