rs3764746

Positions:

• chrX-70038122-G-C

Variant summary

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

The NM_001399.5(EDA):​c.*2513G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 111,175 control chromosomes in the GnomAD database, including 518 homozygotes. There are 2,827 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 0.084 (518 hom., 2824 hem., cov: 22)
  • Exomes 𝑓: 0.094 (0 hom. 3 hem.)
• Consequence: EDA NM_001399.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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]

ENSG00000286077 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDA	NM_001399.5	c.*2513G>C		3_prime_UTR_variant	8/8	ENST00000374552.9	NP_001390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDA	ENST00000374552.9	c.*2513G>C		3_prime_UTR_variant	8/8	1	NM_001399.5	ENSP00000363680.4
EDA	ENST00000374553.6	c.*2513G>C		3_prime_UTR_variant	8/8	1		ENSP00000363681.2
EDA	ENST00000616899.1	c.*2513G>C		3_prime_UTR_variant	7/7	5		ENSP00000481963.1
ENSG00000286077	ENST00000651174.1	n.1045C>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 9328 AN: 111089 Hom.: 506 Cov.: 22 AF XY: 0.0841 AC XY: 2801 AN XY: 33323

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0378

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0907

GnomAD4 exome AF: 0.0938 AC: 3 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.0455

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.0844 AC: 9376 AN: 111143 Hom.: 518 Cov.: 22 AF XY: 0.0846 AC XY: 2824 AN XY: 33387

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.0286

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0544 Hom.: 283

Bravo AF: 0.102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764746; hg19: chrX-69257972;