rs3735935

Positions:

• chr8-71215529-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.593

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]

ACMG classification

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	c.1476-21G>T		intron_variant		ENST00000340726.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48658 AN: 151902 Hom.: 8613 Cov.: 33

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

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.: 33 AF XY: 0.325 AC XY: 236222 AN XY: 725890

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.: 33 AF XY: 0.329 AC XY: 24434 AN XY: 74318

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

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

Other links and lift over

dbSNP: rs3735935; hg19: chr8-72127764; COSMIC: COSV58164182; COSMIC: COSV58164182;