chr6-133247575-T-A

Position:

• chr6-133247575-T-A

Variant summary

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

The NM_004100.5(EYA4):​c.-66+5826T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,188 control chromosomes in the GnomAD database, including 5,446 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 0.25 (5446 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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]

EYA4 (HGNC:):

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 = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA4	NM_004100.5	c.-66+5826T>A		intron_variant		ENST00000355286.12	NP_004091.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA4	ENST00000355286.12	c.-66+5826T>A		intron_variant		1	NM_004100.5	ENSP00000347434.7

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38333 AN: 152068 Hom.: 5440 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.252 AC: 38346 AN: 152186 Hom.: 5446 Cov.: 32 AF XY: 0.261 AC XY: 19390 AN XY: 74404

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.288

Alfa AF: 0.265 Hom.: 743

Bravo AF: 0.251

Asia WGS AF: 0.434 AC: 1507 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.80

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: rs3777781; hg19: chr6-133568713;