rs2520397

chrX-69748833-G-A

Variant summary

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

The NM_001399.5(EDA):c.396+132129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 110,957 control chromosomes in the GnomAD database, including 5,027 homozygotes. There are 10,337 hemizygotes in GnomAD. 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 0.32 (5027 hom., 10337 hem., cov: 22)
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EDA	NM_001399.5	c.396+132129G>A		intron_variant		ENST00000374552.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EDA	ENST00000374552.9	c.396+132129G>A		intron_variant		1	NM_001399.5	P4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 35548 AN: 110907 Hom.: 5034 Cov.: 22 AF XY: 0.312 AC XY: 10329 AN XY: 33149

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.320 AC: 35539 AN: 110957 Hom.: 5027 Cov.: 22 AF XY: 0.311 AC XY: 10337 AN XY: 33209

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.00311

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.352

Alfa AF: 0.374 Hom.: 2573

Bravo AF: 0.305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.7
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2520397; hg19: chrX-68968677;