rs10504503

chr8-71264223-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000503.6(EYA1):c.1050+5517A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 152,268 control chromosomes in the GnomAD database, including 271 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 0.035 (271 hom., cov: 32)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA1	NM_000503.6	c.1050+5517A>G		intron_variant		ENST00000340726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA1	ENST00000340726.8	c.1050+5517A>G		intron_variant		1	NM_000503.6	P4

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5295 AN: 152148 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00996

Gnomad FIN AF: 0.00998

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00403

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0349 AC: 5311 AN: 152268 Hom.: 271 Cov.: 32 AF XY: 0.0345 AC XY: 2571 AN XY: 74454

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00955

Gnomad4 FIN AF: 0.00998

Gnomad4 NFE AF: 0.00403

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0236 Hom.: 54

Bravo AF: 0.0378

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.57
Dann	Benign	0.77

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: rs10504503; hg19: chr8-72176458;