chrX-69666995-A-G

Variant names:

• chrX-69666995-A-G
• rs4844185
• NM_001399.5:c.396+50291A>G

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• tooth agenesis, selective, X-linked, 1

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• X-linked hypohidrotic ectodermal dysplasia

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5	c.396+50291A>G		intron_variant	Intron 1 of 7	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.396+50291A>G		intron_variant	Intron 1 of 7	1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes AF: 0.668 AC: 72984 AN: 109236 Hom.: 17930 Cov.: 23

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

African (AFR) AF: 0.828 AC: 25060 AN: 30260

American (AMR) AF: 0.718 AC: 7352 AN: 10245

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1352 AN: 2622

East Asian (EAS) AF: 0.997 AC: 3518 AN: 3528

South Asian (SAS) AF: 0.730 AC: 1882 AN: 2577

European-Finnish (FIN) AF: 0.612 AC: 3261 AN: 5328

Middle Eastern (MID) AF: 0.436 AC: 88 AN: 202

European-Non Finnish (NFE) AF: 0.556 AC: 29100 AN: 52370

Other (OTH) AF: 0.645 AC: 963 AN: 1494

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
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4844185; hg19: chrX-68886839;