chr6-133274546-C-A

Position:

• chr6-133274546-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004100.5(EYA4):​c.-65-170C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,094 control chromosomes in the GnomAD database, including 3,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3839 hom., cov: 32)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.171

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-133274546-C-A is Benign according to our data. Variant chr6-133274546-C-A is described in ClinVar as [Benign]. Clinvar id is 1296325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA4	NM_004100.5	c.-65-170C>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.-65-170C>A		intron_variant		1	NM_004100.5	ENSP00000347434	P4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32090 AN: 151974 Hom.: 3841 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.211 AC: 32109 AN: 152094 Hom.: 3839 Cov.: 32 AF XY: 0.218 AC XY: 16174 AN XY: 74332

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.235

Alfa AF: 0.195 Hom.: 5627

Bravo AF: 0.217

Asia WGS AF: 0.386 AC: 1339 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
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: rs3734277; hg19: chr6-133595684;