rs11991562

Variant names:

• chr8-71272663-G-A
• rs11991562
• NM_000503.6:c.827-766C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000503.6(EYA1):​c.827-766C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,058 control chromosomes in the GnomAD database, including 5,573 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 0.27 (5573 hom., cov: 32)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• branchio-oto-renal syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• branchiootorenal syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• branchiootic syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• branchiootic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA1	NM_000503.6	c.827-766C>T		intron_variant	Intron 9 of 17	ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.827-766C>T		intron_variant	Intron 9 of 17	1	NM_000503.6	ENSP00000342626.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40880 AN: 151940 Hom.: 5569 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.269 AC: 40912 AN: 152058 Hom.: 5573 Cov.: 32 AF XY: 0.269 AC XY: 19975 AN XY: 74332

African (AFR) AF: 0.252 AC: 10465 AN: 41480

American (AMR) AF: 0.303 AC: 4636 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5164

South Asian (SAS) AF: 0.267 AC: 1289 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2828 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18518 AN: 67974

Other (OTH) AF: 0.259 AC: 547 AN: 2110

Alfa AF: 0.270 Hom.: 17844

Bravo AF: 0.270

Asia WGS AF: 0.272 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.58
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11991562; hg19: chr8-72184898;