rs519332

chr6-133250134-A-Gchr6-133250134-A-T

Variant summary

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

The NM_004100.5(EYA4):c.-66+8385A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,094 control chromosomes in the GnomAD database, including 48,820 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 0.80 (48820 hom., cov: 31)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467

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]

LOC124901231 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA4	NM_004100.5	c.-66+8385A>G		intron_variant		ENST00000355286.12
LOC124901231	XM_047419612.1	c.82+3379T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA4	ENST00000355286.12	c.-66+8385A>G		intron_variant		1	NM_004100.5	P4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121124 AN: 151976 Hom.: 48776 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.797 AC: 121223 AN: 152094 Hom.: 48820 Cov.: 31 AF XY: 0.798 AC XY: 59284 AN XY: 74322

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.772

Alfa AF: 0.756 Hom.: 11330

Bravo AF: 0.805

Asia WGS AF: 0.856 AC: 2974 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	0.12
Dann	Benign	0.38

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: rs519332; hg19: chr6-133571272;