rs13263568

Variant names:

• chr8-71535183-T-G
• rs13263568
• ENST00000523987.4:n.248+561A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370333.1(EYA1):​c.33+561A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 152,286 control chromosomes in the GnomAD database, including 498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.072 (498 hom., cov: 32)
• Consequence: EYA1 NM_001370333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• Publications: 10 publications found

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: Orphanet, ClinGen
• branchiootorenal syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• branchiootic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370333.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	NM_001370333.1		c.33+561A>C		intron	N/A	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.-129+561A>C		intron	N/A	NP_001357263.1	Q99502-1
	EYA1	NM_001370335.1		c.-344+561A>C		intron	N/A	NP_001357264.1	Q99502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	ENST00000523987.4	TSL:1	n.248+561A>C		intron	N/A
	EYA1	ENST00000643681.1		c.33+561A>C		intron	N/A	ENSP00000495390.1	A0A2R8Y6K4
	EYA1	ENST00000645793.1		c.-344+561A>C		intron	N/A	ENSP00000496255.1	Q99502-1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10961 AN: 152168 Hom.: 499 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0493

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.0712

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0719 AC: 10952 AN: 152286 Hom.: 498 Cov.: 32 AF XY: 0.0705 AC XY: 5250 AN XY: 74444

African (AFR) AF: 0.0311 AC: 1295 AN: 41574

American (AMR) AF: 0.0613 AC: 937 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3472

East Asian (EAS) AF: 0.120 AC: 622 AN: 5172

South Asian (SAS) AF: 0.125 AC: 605 AN: 4834

European-Finnish (FIN) AF: 0.0493 AC: 523 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0960 AC: 6530 AN: 68010

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

Alfa AF: 0.0826 Hom.: 416

Bravo AF: 0.0685

Asia WGS AF: 0.108 AC: 374 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.013
DANN	Benign	0.67
PhyloP100		-3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13263568; hg19: chr8-72447418;