rs13260349

Variant names:

• chr8-71224626-C-T
• rs13260349
• NM_000503.6:c.1141-7603G>A

Variant summary

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

The NM_000503.6(EYA1):​c.1141-7603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,104 control chromosomes in the GnomAD database, including 14,631 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 0.42 (14631 hom., cov: 33)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 3 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

ENSG00000285579 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000503.6. 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_000503.6	MANE Select	c.1141-7603G>A		intron	N/A	NP_000494.2
	EYA1	NM_001370333.1		c.1228-7603G>A		intron	N/A	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.1141-7603G>A		intron	N/A	NP_001357263.1	Q99502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	ENST00000340726.8	TSL:1 MANE Select	c.1141-7603G>A		intron	N/A	ENSP00000342626.3	Q99502-1
	EYA1	ENST00000388742.8	TSL:1	c.1141-7603G>A		intron	N/A	ENSP00000373394.4	Q99502-1
	EYA1	ENST00000419131.6	TSL:1	c.1036-7603G>A		intron	N/A	ENSP00000410176.1	Q99502-3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64533 AN: 151986 Hom.: 14617 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.425 AC: 64578 AN: 152104 Hom.: 14631 Cov.: 33 AF XY: 0.419 AC XY: 31179 AN XY: 74352

African (AFR) AF: 0.570 AC: 23649 AN: 41492

American (AMR) AF: 0.343 AC: 5248 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3466

East Asian (EAS) AF: 0.115 AC: 597 AN: 5176

South Asian (SAS) AF: 0.211 AC: 1019 AN: 4824

European-Finnish (FIN) AF: 0.401 AC: 4252 AN: 10594

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26985 AN: 67964

Other (OTH) AF: 0.422 AC: 890 AN: 2108

Alfa AF: 0.400 Hom.: 6427

Bravo AF: 0.425

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.78
DANN	Benign	0.56
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13260349; hg19: chr8-72136861;