rs454877

chr6-133290087-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004100.5(EYA4):c.33+15274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,792 control chromosomes in the GnomAD database, including 6,883 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 0.30 (6883 hom., cov: 32)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

Genes affected

EYA4 (HGNC:3522): (EYA transcriptional coactivator and phosphatase 4) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator through its protein phosphatase activity, and it may be important for eye development, and for continued function of the mature organ of Corti. Mutations in this gene are associated with postlingual, progressive, autosomal dominant hearing loss at the deafness, autosomal dominant non-syndromic sensorineural 10 locus. The encoded protein is also a putative oncogene that mediates DNA repair, apoptosis, and innate immunity following DNA damage, cellular damage, and viral attack. Defects in this gene are also associated with dilated cardiomyopathy 1J. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA4	NM_004100.5	c.33+15274C>T		intron_variant		ENST00000355286.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA4	ENST00000355286.12	c.33+15274C>T		intron_variant		1	NM_004100.5	P4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44858 AN: 151674 Hom.: 6873 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.296 AC: 44898 AN: 151792 Hom.: 6883 Cov.: 32 AF XY: 0.293 AC XY: 21715 AN XY: 74158

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.276

Alfa AF: 0.305 Hom.: 923

Bravo AF: 0.292

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.60

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: rs454877; hg19: chr6-133611225; COSMIC: COSV62059428;