rs2380716

Positions:

• chr8-71262179-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+7561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,166 control chromosomes in the GnomAD database, including 1,117 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 0.12 (1117 hom., cov: 32)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA1	NM_000503.6	c.1050+7561A>G		intron_variant		ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.1050+7561A>G		intron_variant		1	NM_000503.6	ENSP00000342626.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17758 AN: 152048 Hom.: 1117 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.0704

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.117 AC: 17770 AN: 152166 Hom.: 1117 Cov.: 32 AF XY: 0.114 AC XY: 8465 AN XY: 74388

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0719

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0964

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.0910

Alfa AF: 0.120 Hom.: 564

Bravo AF: 0.115

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.48

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: rs2380716; hg19: chr8-72174414;