rs2804391

Variant names:

• chrX-69765858-T-C
• rs2804391
• NM_001399.5:c.396+149154T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001399.5(EDA):​c.396+149154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 110,557 control chromosomes in the GnomAD database, including 4,883 homozygotes. There are 10,089 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 (4883 hom., 10089 hem., cov: 22)
• Consequence: EDA NM_001399.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5	c.396+149154T>C		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+149154T>C		intron_variant	Intron 1 of 7	1	NM_001399.5	ENSP00000363680.4

Frequencies

GnomAD3 genomes AF: 0.317 AC: 34984 AN: 110503 Hom.: 4889 Cov.: 22

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.00284

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.575

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.316 AC: 34975 AN: 110557 Hom.: 4883 Cov.: 22 AF XY: 0.307 AC XY: 10089 AN XY: 32821

African (AFR) AF: 0.131 AC: 4014 AN: 30597

American (AMR) AF: 0.274 AC: 2844 AN: 10375

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1273 AN: 2623

East Asian (EAS) AF: 0.00284 AC: 10 AN: 3516

South Asian (SAS) AF: 0.258 AC: 672 AN: 2606

European-Finnish (FIN) AF: 0.384 AC: 2215 AN: 5762

Middle Eastern (MID) AF: 0.559 AC: 119 AN: 213

European-Non Finnish (NFE) AF: 0.438 AC: 23091 AN: 52686

Other (OTH) AF: 0.353 AC: 532 AN: 1505

Alfa AF: 0.363 Hom.: 2786

Bravo AF: 0.302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.60
PhyloP100		0.24
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: rs2804391; hg19: chrX-68985702;