rs4738118

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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 (★★). Synonymous variant affecting the same amino acid position (i.e. GG426GG?) has been classified as Pathogenic.

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

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 links:

ENSG00000285579 (HGNC:):

ENSG00000285579 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 48101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-71216774-G-A is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.219

AC:

54973

AN:

251276

Hom.:

9606

AF XY:

0.215

AC XY:

29190

AN XY:

135800

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 SAS exome

AF:

0.321

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

Gnomad4 AFR exome

AF:

0.0875

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.670

Gnomad4 SAS exome

AF:

0.310

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.152

AC:

23074

AN:

152052

Hom.:

2843

Cov.:

AF XY:

0.161

AC XY:

11981

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0922

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.656

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.123

Hom.:

2210

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

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

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). -

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

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

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

DANN

Benign

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over