X-69666995-A-G

Position:

• chrX-69666995-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001399.5(EDA):​c.396+50291A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.67 (17935 hom., 21427 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

Genes affected

EDA (HGNC:3157): (ectodysplasin A) The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

EDA (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA	NM_001399.5	c.396+50291A>G		intron_variant		ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.396+50291A>G		intron_variant		1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 72984 AN: 109236 Hom.: 17930 Cov.: 23 AF XY: 0.675 AC XY: 21381 AN XY: 31658

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.640

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.668 AC: 73036 AN: 109285 Hom.: 17935 Cov.: 23 AF XY: 0.676 AC XY: 21427 AN XY: 31715

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.645

Alfa AF: 0.398 Hom.: 1604

Bravo AF: 0.683

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.6
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4844185; hg19: chrX-68886839;