Genetic Variant EYA3:c.994-9G>A (chr1-28000058-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001990.4(EYA3):c.994-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,578,884 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 80 hom. )

Consequence

EYA3
NM_001990.4 intron

Scores

Splicing: ADA: 0.0002758

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.426

Publications

1 publications found

Variant links:

Genes affected

EYA3 (HGNC:3521): (EYA transcriptional coactivator and phosphatase 3) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator and have a role during development. It can act as a mediator of chemoresistance and cell survival in Ewing sarcoma cells, where this gene is up-regulated via a micro-RNA that binds to the 3' UTR of the transcript. A similar protein in mice acts as a transcriptional activator. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2013]

EYA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-28000058-C-T is Benign according to our data. Variant chr1-28000058-C-T is described in ClinVar as Benign. ClinVar VariationId is 736351.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00104 (159/152242) while in subpopulation SAS AF = 0.03 (145/4830). AF 95% confidence interval is 0.026. There are 3 homozygotes in GnomAd4. There are 106 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 159 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYA3	NM_001990.4	MANE Select	c.994-9G>A	intron	N/A	NP_001981.2
EYA3	NM_001282560.2		c.856-9G>A	intron	N/A	NP_001269489.1	Q99504-3
EYA3	NM_001282561.2		c.856-9G>A	intron	N/A	NP_001269490.1	Q99504-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYA3	ENST00000373871.8	TSL:1 MANE Select	c.994-9G>A	intron	N/A	ENSP00000362978.3	Q99504-1
EYA3	ENST00000373863.3	TSL:1	c.856-9G>A	intron	N/A	ENSP00000362970.3	Q99504-3
EYA3	ENST00000471498.5	TSL:1	n.1136-9G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

159

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00411

AC:

908

AN:

220666

AF XY:

0.00547

show subpopulations

Gnomad AFR exome

AF:

0.0000664

Gnomad AMR exome

AF:

0.000158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000946

Gnomad NFE exome

AF:

0.0000665

Gnomad OTH exome

AF:

0.00174

GnomAD4 exome

AF:

0.00207

AC:

2949

AN:

1426642

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

2084

AN XY:

709590

show subpopulations

African (AFR)

AF:

0.000159

AC:

AN:

31540

American (AMR)

AF:

0.000215

AC:

AN:

37144

Ashkenazi Jewish (ASJ)

AF:

0.0000798

AC:

AN:

25062

East Asian (EAS)

AF:

0.00

AC:

AN:

38522

South Asian (SAS)

AF:

0.0342

AC:

2712

AN:

79388

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

53070

Middle Eastern (MID)

AF:

0.00230

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0000738

AC:

AN:

1097282

Other (OTH)

AF:

0.00209

AC:

123

AN:

58984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

127

254

380

507

634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00104

AC:

159

AN:

152242

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41542

American (AMR)

AF:

0.000458

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0300

AC:

145

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000284

Hom.:

Bravo

AF:

0.000385

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.0

(source)

DANN

Benign

0.48

PhyloP100

-0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.012

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over