1-236409544-T-G

Position:

• chr1-236409544-T-G

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.120+270T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 146,862 control chromosomes in the GnomAD database, including 31,197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (31197 hom., cov: 29)
• Consequence: EDARADD NM_145861.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.826

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=-0.9).
• BP6: Variant 1-236409544-T-G is Benign according to our data. Variant chr1-236409544-T-G is described in ClinVar as [Benign]. Clinvar id is 1295851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDARADD	NM_145861.4	c.120+270T>G		intron_variant		ENST00000334232.9	NP_665860.2
EDARADD	NM_080738.4	c.90+270T>G		intron_variant			NP_542776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDARADD	ENST00000334232.9	c.120+270T>G		intron_variant		1	NM_145861.4	ENSP00000335076

Frequencies

GnomAD3 genomes AF: 0.654 AC: 96025 AN: 146758 Hom.: 31151 Cov.: 29

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.655 AC: 96129 AN: 146862 Hom.: 31197 Cov.: 29 AF XY: 0.656 AC XY: 47171 AN XY: 71900

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.648

Alfa AF: 0.678 Hom.: 7146

Bravo AF: 0.617

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

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.37

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: rs671040; hg19: chr1-236572844;