rs1481800

Positions:

• chr8-71219191-G-A
• chr8-71219191-G-C
• chr8-71219191-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000503.6(EYA1):​c.1141-2168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,892 control chromosomes in the GnomAD database, including 16,555 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 0.43 (16555 hom., cov: 32)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA1	NM_000503.6	c.1141-2168C>T		intron_variant		ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.1141-2168C>T		intron_variant		1	NM_000503.6	ENSP00000342626.3

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65047 AN: 151776 Hom.: 16495 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.429 AC: 65168 AN: 151892 Hom.: 16555 Cov.: 32 AF XY: 0.435 AC XY: 32260 AN XY: 74212

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.403

Alfa AF: 0.302 Hom.: 10911

Bravo AF: 0.447

Asia WGS AF: 0.660 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.74

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: rs1481800; hg19: chr8-72131426;