rs373910569

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_004100.5(EYA4):c.1197C>A(p.Pro399Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P399P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EYA4
NM_004100.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0710

Publications

1 publications found

Variant links:

Genes affected

EYA4 (HGNC:3522): (EYA transcriptional coactivator and phosphatase 4) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

EYA4 links:

TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

TARID links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 6-133506111-C-A is Benign according to our data. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-133506111-C-A is described in CliVar as Likely_benign. Clinvar id is 1618028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.071 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA4	NM_004100.5 link	c.1197C>A	p.Pro399Pro	synonymous_variant	Exon 14 of 20	ENST00000355286.12	NP_004091.3	O95677-1Q96CJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA4	ENST00000355286.12 link	c.1197C>A	p.Pro399Pro	synonymous_variant	Exon 14 of 20	1	NM_004100.5	ENSP00000347434.7		O95677-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251188

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1444492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719866

African (AFR)

AF:

0.00

AC:

AN:

33142

American (AMR)

AF:

0.00

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39600

South Asian (SAS)

AF:

0.00

AC:

AN:

85922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096192

Other (OTH)

AF:

0.00

AC:

AN:

59840

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1J

Benign:1

Dec 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 13, 2020

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

-0.071

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over