rs4738119

Positions:

• chr8-71220245-C-A
• chr8-71220245-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	Protein	UniProt
EYA1	NM_000503.6	c.1141-3222G>T		intron_variant		ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.1141-3222G>T		intron_variant		1	NM_000503.6	ENSP00000342626	P4

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

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.892

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.594

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

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: rs4738119; hg19: chr8-72132480;