X-69673072-G-A

Position:

• chrX-69673072-G-A

Variant summary

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

The NM_001399.5(EDA):​c.396+56368G>A 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 0.66 (17624 hom., 20881 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA	NM_001399.5	c.396+56368G>A		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+56368G>A		intron_variant		1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 72092 AN: 109613 Hom.: 17619 Cov.: 22 AF XY: 0.654 AC XY: 20830 AN XY: 31847

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.628

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: 0.658 AC: 72148 AN: 109663 Hom.: 17624 Cov.: 22 AF XY: 0.654 AC XY: 20881 AN XY: 31907

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.633

Alfa AF: 0.565 Hom.: 63760

Bravo AF: 0.677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.93
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5936487; hg19: chrX-68892916;