rs6940715

Positions:

• chr6-133280707-A-C
• chr6-133280707-A-G

Variant summary

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

The NM_004100.5(EYA4):​c.33+5894A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,192 control chromosomes in the GnomAD database, including 1,018 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 0.11 (1018 hom., cov: 32)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA4	NM_004100.5	c.33+5894A>C		intron_variant		ENST00000355286.12	NP_004091.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA4	ENST00000355286.12	c.33+5894A>C		intron_variant		1	NM_004100.5	ENSP00000347434	P4

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16610 AN: 152074 Hom.: 1017 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0680

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0877

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

GnomAD4 genome AF: 0.109 AC: 16631 AN: 152192 Hom.: 1018 Cov.: 32 AF XY: 0.109 AC XY: 8082 AN XY: 74410

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0679

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.0542 Hom.: 62

Bravo AF: 0.105

Asia WGS AF: 0.0460 AC: 163 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	6.0
DANN	Benign	0.70

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: rs6940715; hg19: chr6-133601845;