NM_000503.6:c.1141-3222G>T

Variant names:

• chr8-71220245-C-A
• rs4738119
• NM_000503.6:c.1141-3222G>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.1141-3222G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,088 control chromosomes in the GnomAD database, including 28,728 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 0.60 (28728 hom., cov: 33)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.188
• Publications: 5 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

ENSG00000285579 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA1	NM_000503.6	c.1141-3222G>T		intron_variant	Intron 12 of 17	ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.1141-3222G>T		intron_variant	Intron 12 of 17	1	NM_000503.6	ENSP00000342626.3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91550 AN: 151970 Hom.: 28666 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.603 AC: 91678 AN: 152088 Hom.: 28728 Cov.: 33 AF XY: 0.609 AC XY: 45280 AN XY: 74334

African (AFR) AF: 0.747 AC: 30998 AN: 41508

American (AMR) AF: 0.618 AC: 9443 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3470

East Asian (EAS) AF: 0.892 AC: 4622 AN: 5184

South Asian (SAS) AF: 0.691 AC: 3332 AN: 4822

European-Finnish (FIN) AF: 0.563 AC: 5933 AN: 10544

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33653 AN: 67968

Other (OTH) AF: 0.594 AC: 1253 AN: 2110

Alfa AF: 0.532 Hom.: 4501

Bravo AF: 0.612

Asia WGS AF: 0.801 AC: 2786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.9
DANN	Benign	0.66
PhyloP100		0.19
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: rs4738119; hg19: chr8-72132480;