rs13260349

Positions:

• chr8-71224626-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA1	NM_000503.6	c.1141-7603G>A		intron_variant		ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.1141-7603G>A		intron_variant		1	NM_000503.6	ENSP00000342626.3

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

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.422

Alfa AF: 0.413 Hom.: 4428

Bravo AF: 0.425

Asia WGS AF: 0.191 AC: 665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.78
DANN	Benign	0.56

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: rs13260349; hg19: chr8-72136861;