rs11154727

Variant names:

• chr6-133454984-T-C
• rs11154727
• NM_004100.5:c.278-1572T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-133454984-T-C
• chr6-133454984-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000355286.12(EYA4):​c.278-1572T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,060 control chromosomes in the GnomAD database, including 2,714 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 0.18 (2714 hom., cov: 32)
• Consequence: EYA4 ENST00000355286.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy 1J

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen

ENSG00000234567 (HGNC:58230):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355286.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA4	NM_004100.5	MANE Select	c.278-1572T>C		intron	N/A	NP_004091.3
	EYA4	NM_001301013.2		c.278-1572T>C		intron	N/A	NP_001287942.1
	EYA4	NM_172105.4		c.278-1572T>C		intron	N/A	NP_742103.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA4	ENST00000355286.12	TSL:1 MANE Select	c.278-1572T>C		intron	N/A	ENSP00000347434.7
	EYA4	ENST00000531901.5	TSL:2	c.278-1572T>C		intron	N/A	ENSP00000432770.1
	EYA4	ENST00000431403.3	TSL:5	c.209-1572T>C		intron	N/A	ENSP00000404558.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27258 AN: 151940 Hom.: 2717 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.179 AC: 27250 AN: 152060 Hom.: 2714 Cov.: 32 AF XY: 0.181 AC XY: 13462 AN XY: 74340

African (AFR) AF: 0.106 AC: 4413 AN: 41538

American (AMR) AF: 0.176 AC: 2683 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.322 AC: 1656 AN: 5150

South Asian (SAS) AF: 0.247 AC: 1194 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2168 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13614 AN: 67934

Other (OTH) AF: 0.201 AC: 423 AN: 2106

Alfa AF: 0.193 Hom.: 4986

Bravo AF: 0.178

Asia WGS AF: 0.279 AC: 970 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.60
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11154727; hg19: chr6-133776122;