rs9321395

chr6-133280124-G-Achr6-133280124-G-C

Variant summary

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

The NM_004100.5(EYA4):c.33+5311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 151,946 control chromosomes in the GnomAD database, including 6,349 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 (6349 hom., cov: 32)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA4	NM_004100.5	c.33+5311G>A		intron_variant		ENST00000355286.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA4	ENST00000355286.12	c.33+5311G>A		intron_variant		1	NM_004100.5	P4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41528 AN: 151828 Hom.: 6345 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.274 AC: 41575 AN: 151946 Hom.: 6349 Cov.: 32 AF XY: 0.279 AC XY: 20750 AN XY: 74302

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.297

Alfa AF: 0.240 Hom.: 1232

Bravo AF: 0.289

Asia WGS AF: 0.435 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	9.9
Dann	Benign	0.84

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: rs9321395; hg19: chr6-133601262;