rs10103397

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.1755T>C(p.His585His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,610,680 control chromosomes in the GnomAD database, including 100,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10508 hom., cov: 32)

Exomes 𝑓: 0.34 ( 90491 hom. )

Consequence

EYA1
NM_000503.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.426

Publications

28 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:

ENSG00000254031 (HGNC:):

ENSG00000254031 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=-0.88).

BP6

Variant 8-71199364-A-G is Benign according to our data. Variant chr8-71199364-A-G is described in ClinVar as Benign. ClinVar VariationId is 48107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.426 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA1	NM_000503.6 link	c.1755T>C	p.His585His	synonymous_variant	Exon 18 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.1755T>C	p.His585His	synonymous_variant	Exon 18 of 18	1	NM_000503.6	ENSP00000342626.3		Q99502-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54678

AN:

151900

Hom.:

10476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.446

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.360

GnomAD2 exomes

AF:

0.396

AC:

98291

AN:

248410

AF XY:

0.389

show subpopulations

Gnomad AFR exome

AF:

0.350

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.780

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.339

AC:

493791

AN:

1458662

Hom.:

90491

Cov.:

AF XY:

0.340

AC XY:

246908

AN XY:

725630

show subpopulations

African (AFR)

AF:

0.352

AC:

11778

AN:

33426

American (AMR)

AF:

0.513

AC:

22897

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

9323

AN:

26116

East Asian (EAS)

AF:

0.784

AC:

31050

AN:

39620

South Asian (SAS)

AF:

0.449

AC:

38651

AN:

86026

European-Finnish (FIN)

AF:

0.339

AC:

17883

AN:

52778

Middle Eastern (MID)

AF:

0.304

AC:

1750

AN:

5764

European-Non Finnish (NFE)

AF:

0.305

AC:

338892

AN:

1110010

Other (OTH)

AF:

0.358

AC:

21567

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

15547

31093

46640

62186

77733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11538

23076

34614

46152

57690

<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:

0.360

AC:

54766

AN:

152018

Hom.:

10508

Cov.:

AF XY:

0.368

AC XY:

27327

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.354

AC:

14667

AN:

41420

American (AMR)

AF:

0.439

AC:

6712

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

1215

AN:

3468

East Asian (EAS)

AF:

0.778

AC:

4027

AN:

5178

South Asian (SAS)

AF:

0.484

AC:

2335

AN:

4820

European-Finnish (FIN)

AF:

0.370

AC:

3911

AN:

10558

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.303

AC:

20615

AN:

67982

Other (OTH)

AF:

0.368

AC:

775

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1731

3462

5192

6923

8654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.315

Hom.:

2628

Bravo

AF:

0.366

Asia WGS

AF:

0.637

AC:

2215

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The His585His variant is a common benign variant present in ~40% of the African population, ~75% of the Asian population, ~20% of the Caucasian population (dbSN P - rs10103397). -

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

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

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

Branchiootic syndrome 1

Benign:2

Jan 13, 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. -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Otofaciocervical syndrome 1

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Branchiootorenal syndrome 1

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

-0.88

CADD

Benign

0.14

(source)

DANN

Benign

0.50

PhyloP100

-0.43

Mutation Taster

=99/1

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