rs13263568

Positions:

• chr8-71535183-T-G

Variant summary

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

The ENST00000523987.4(EYA1):​n.248+561A>C variant causes a intron, non coding transcript 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 ENST00000523987.4 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA1	NM_001370333.1	c.33+561A>C		intron_variant
EYA1	NM_001370334.1	c.-129+561A>C		intron_variant
EYA1	NM_001370335.1	c.-344+561A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA1	ENST00000523987.4	n.248+561A>C		intron_variant, non_coding_transcript_variant		1
EYA1	ENST00000643681.1	c.33+561A>C		intron_variant
EYA1	ENST00000644229.1	c.33+561A>C		intron_variant

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

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0493

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0903 Hom.: 370

Bravo AF: 0.0685

Asia WGS AF: 0.108 AC: 374 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13263568; hg19: chr8-72447418;