chr8-71351721-C-T

Variant names:

• chr8-71351721-C-T
• rs2218488
• NM_000503.6:c.124+3061G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000503.6(EYA1):​c.124+3061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,210 control chromosomes in the GnomAD database, including 53,098 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 0.83 (53098 hom., cov: 33)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 16 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA1	NM_000503.6	c.124+3061G>A		intron_variant	Intron 3 of 17	ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.124+3061G>A		intron_variant	Intron 3 of 17	1	NM_000503.6	ENSP00000342626.3

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126993 AN: 152092 Hom.: 53072 Cov.: 33

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.835 AC: 127075 AN: 152210 Hom.: 53098 Cov.: 33 AF XY: 0.837 AC XY: 62274 AN XY: 74424

African (AFR) AF: 0.828 AC: 34389 AN: 41510

American (AMR) AF: 0.877 AC: 13409 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2986 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4332 AN: 5174

South Asian (SAS) AF: 0.794 AC: 3834 AN: 4830

European-Finnish (FIN) AF: 0.857 AC: 9095 AN: 10610

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56180 AN: 67994

Other (OTH) AF: 0.851 AC: 1800 AN: 2116

Alfa AF: 0.829 Hom.: 222980

Bravo AF: 0.835

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.65
PhyloP100		1.2
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: rs2218488; hg19: chr8-72263956;