Genetic Variant EDA:c.*3056T>G (chrX-70038665-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001399.5(EDA):c.*3056T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 111,085 control chromosomes in the GnomAD database, including 4,767 homozygotes. There are 10,912 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 0.33 ( 4750 hom., 10851 hem., cov: 22)

Exomes 𝑓: 0.48 ( 17 hom. 61 hem. )

Consequence

EDA
NM_001399.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

3 publications found

Variant links:

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

EDA links:

ENSG00000286077 (HGNC:):

ENSG00000286077 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDA	NM_001399.5 link	c.*3056T>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000374552.9	NP_001390.1	Q92838-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EDA	ENST00000374552.9 link	c.*3056T>G	3_prime_UTR_variant	Exon 8 of 8	1	NM_001399.5	ENSP00000363680.4	Q92838-1
EDA	ENST00000374553.6 link	c.*3056T>G	3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000363681.2	Q92838-3
ENSG00000286077	ENST00000651174.1 link	n.502A>C	non_coding_transcript_exon_variant	Exon 2 of 2
EDA	ENST00000616899.1 link	c.*3056T>G	3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000481963.1	A0A0C4DGX3

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

36354

AN:

110718

Hom.:

4738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.523

Gnomad SAS

AF:

0.479

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.302

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.352

GnomAD4 exome

AF:

0.477

AC:

147

AN:

308

Hom.:

Cov.:

AF XY:

0.455

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.480

AC:

143

AN:

298

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.329

AC:

36398

AN:

110777

Hom.:

4750

Cov.:

AF XY:

0.329

AC XY:

10851

AN XY:

33011

show subpopulations

African (AFR)

AF:

0.158

AC:

4843

AN:

30600

American (AMR)

AF:

0.465

AC:

4859

AN:

10445

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

756

AN:

2625

East Asian (EAS)

AF:

0.524

AC:

1810

AN:

3454

South Asian (SAS)

AF:

0.480

AC:

1228

AN:

2560

European-Finnish (FIN)

AF:

0.424

AC:

2484

AN:

5864

Middle Eastern (MID)

AF:

0.285

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.369

AC:

19472

AN:

52831

Other (OTH)

AF:

0.361

AC:

544

AN:

1509

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

837

1673

2510

3346

4183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.339

Hom.:

23750

Bravo

AF:

0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.015

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over