rs212769

Positions:

• chr6-133452410-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.278-4146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,952 control chromosomes in the GnomAD database, including 14,140 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 0.38 (14140 hom., cov: 32)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA4	NM_004100.5	c.278-4146C>T		intron_variant		ENST00000355286.12	NP_004091.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA4	ENST00000355286.12	c.278-4146C>T		intron_variant		1	NM_004100.5	ENSP00000347434.7

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58017 AN: 151834 Hom.: 14148 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.382 AC: 58020 AN: 151952 Hom.: 14140 Cov.: 32 AF XY: 0.381 AC XY: 28289 AN XY: 74294

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.383

Alfa AF: 0.457 Hom.: 2249

Bravo AF: 0.348

Asia WGS AF: 0.214 AC: 745 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.50

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: rs212769; hg19: chr6-133773548;