rs4738118

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000503.6(EYA1):c.1278C>T(p.Gly426Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,682 control chromosomes in the GnomAD database, including 28,388 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2843 hom., cov: 32)

Exomes 𝑓: 0.15 ( 25545 hom. )

Consequence

EYA1
NM_000503.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.136

Publications

26 publications found

Variant links:

Genes affected

EYA1 (HGNC:3519): (EYA transcriptional coactivator and phosphatase 1) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations of this gene have been associated with branchiootorenal dysplasia syndrome, branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies. A similar protein in mice can act as a transcriptional activator. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2013]

EYA1 Gene-Disease associations (from GenCC):

branchio-oto-renal syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
branchiootorenal syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
branchiootic syndrome 1
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
branchiootic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EYA1 links:

ENSG00000285579 (HGNC:):

ENSG00000285579 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 8-71216774-G-A is Benign according to our data. Variant chr8-71216774-G-A is described in ClinVar as Benign. ClinVar VariationId is 48101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.136 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA1	NM_000503.6 link	c.1278C>T	p.Gly426Gly	synonymous_variant	Exon 14 of 18	ENST00000340726.8	NP_000494.2	Q99502-1A0A024R813B3KXR1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8 link	c.1278C>T	p.Gly426Gly	synonymous_variant	Exon 14 of 18	1	NM_000503.6	ENSP00000342626.3		Q99502-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23031

AN:

151934

Hom.:

2833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0921

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.149

GnomAD2 exomes

AF:

0.219

AC:

54973

AN:

251276

AF XY:

0.215

show subpopulations

Gnomad AFR exome

AF:

0.0902

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.143

Gnomad EAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.149

AC:

218212

AN:

1461630

Hom.:

25545

Cov.:

AF XY:

0.153

AC XY:

110966

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.0875

AC:

2930

AN:

33474

American (AMR)

AF:

0.342

AC:

15274

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

3804

AN:

26134

East Asian (EAS)

AF:

0.670

AC:

26582

AN:

39694

South Asian (SAS)

AF:

0.310

AC:

26761

AN:

86258

European-Finnish (FIN)

AF:

0.158

AC:

8419

AN:

53412

Middle Eastern (MID)

AF:

0.117

AC:

673

AN:

5766

European-Non Finnish (NFE)

AF:

0.111

AC:

123475

AN:

1111788

Other (OTH)

AF:

0.170

AC:

10294

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9641

19281

28922

38562

48203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4926

9852

14778

19704

24630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.152

AC:

23074

AN:

152052

Hom.:

2843

Cov.:

AF XY:

0.161

AC XY:

11981

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0922

AC:

3825

AN:

41486

American (AMR)

AF:

0.240

AC:

3665

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

480

AN:

3472

East Asian (EAS)

AF:

0.656

AC:

3386

AN:

5158

South Asian (SAS)

AF:

0.355

AC:

1706

AN:

4810

European-Finnish (FIN)

AF:

0.161

AC:

1703

AN:

10576

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7721

AN:

67964

Other (OTH)

AF:

0.157

AC:

332

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

894

1789

2683

3578

4472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.127

Hom.:

4208

Bravo

AF:

0.155

Asia WGS

AF:

0.513

AC:

1781

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 24, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The Gly426Gly variant in EYA1 is a silent common benign variant present in ~10% of Caucasian and African populations, and in >50% of Asian populations (dbSNP- r s4738118). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Branchiootic syndrome 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Melnick-Fraser syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Otofaciocervical syndrome 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.0

(source)

DANN

Benign

0.54

PhyloP100

-0.14

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over