rs7006821

Positions:

• chr8-71357847-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.-54-1336A>G variant causes a intron change. The variant allele was found at a frequency of 0.0887 in 152,240 control chromosomes in the GnomAD database, including 789 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 0.089 (789 hom., cov: 33)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA1	NM_000503.6	c.-54-1336A>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.-54-1336A>G		intron_variant		1	NM_000503.6	ENSP00000342626	P4

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13491 AN: 152122 Hom.: 784 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0887 AC: 13510 AN: 152240 Hom.: 789 Cov.: 33 AF XY: 0.0859 AC XY: 6397 AN XY: 74438

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0670 Hom.: 505

Bravo AF: 0.0893

Asia WGS AF: 0.0270 AC: 94 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7006821; hg19: chr8-72270082;