chr6-133342451-C-T

Position:

• chr6-133342451-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.34-39941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 147,280 control chromosomes in the GnomAD database, including 5,267 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 0.24 (5267 hom., cov: 23)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740

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 = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA4	NM_004100.5	c.34-39941C>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.34-39941C>T		intron_variant		1	NM_004100.5	ENSP00000347434	P4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 34611 AN: 147182 Hom.: 5265 Cov.: 23

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.235 AC: 34617 AN: 147280 Hom.: 5267 Cov.: 23 AF XY: 0.237 AC XY: 17003 AN XY: 71848

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.259

Alfa AF: 0.313 Hom.: 6756

Bravo AF: 0.219

Asia WGS AF: 0.158 AC: 551 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.62

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: rs11753937; hg19: chr6-133663589; COSMIC: COSV62061520;