Variant 8-71215529-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000503.6(EYA1):c.1476-21G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,610,736 control chromosomes in the GnomAD database, including 91,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8629 hom., cov: 33)

Exomes 𝑓: 0.32 ( 83186 hom. )

Consequence

EYA1
NM_000503.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.593

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-71215529-C-A is Benign according to our data. Variant chr8-71215529-C-A is described in ClinVar as [Benign]. Clinvar id is 1253275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-71215529-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA1	NM_000503.6 linkuse as main transcript	c.1476-21G>T		intron_variant		ENST00000340726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA1	ENST00000340726.8 linkuse as main transcript	c.1476-21G>T		intron_variant		1	NM_000503.6	P4	Q99502-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48658

AN:

151902

Hom.:

8613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.413

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.758

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.378

AC:

94834

AN:

250698

Hom.:

20585

AF XY:

0.374

AC XY:

50644

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.761

Gnomad SAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.323

AC:

471592

AN:

1458716

Hom.:

83186

Cov.:

AF XY:

0.325

AC XY:

236222

AN XY:

725890

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.758

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.320

AC:

48712

AN:

152020

Hom.:

8629

Cov.:

AF XY:

0.329

AC XY:

24434

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.339

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.469

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.333

Alfa

AF:

0.274

Hom.:

3107

Bravo

AF:

0.322

Asia WGS

AF:

0.615

AC:

2142

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Branchiootic syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Branchiootorenal syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Otofaciocervical syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.3

DANN

Benign

0.67

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