6-133506010-T-C

Position:

• chr6-133506010-T-C

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.1192-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 800,300 control chromosomes in the GnomAD database, including 345,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (66902 hom., cov: 31)
  • Exomes 𝑓: 0.93 (278533 hom.)
• Consequence: EYA4 NM_004100.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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]

TARID (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-133506010-T-C is Benign according to our data. Variant chr6-133506010-T-C is described in ClinVar as [Benign]. Clinvar id is 1296321.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA4	NM_004100.5	c.1192-96T>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.1192-96T>C		intron_variant		1	NM_004100.5	ENSP00000347434.7

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142439 AN: 152098 Hom.: 66839 Cov.: 31

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.911

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.937

GnomAD4 exome AF: 0.926 AC: 600410 AN: 648084 Hom.: 278533 AF XY: 0.929 AC XY: 325497 AN XY: 350474

Gnomad4 AFR exome AF: 0.983

Gnomad4 AMR exome AF: 0.958

Gnomad4 ASJ exome AF: 0.964

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.983

Gnomad4 FIN exome AF: 0.911

Gnomad4 NFE exome AF: 0.903

Gnomad4 OTH exome AF: 0.930

GnomAD4 genome AF: 0.937 AC: 142563 AN: 152216 Hom.: 66902 Cov.: 31 AF XY: 0.939 AC XY: 69891 AN XY: 74422

Gnomad4 AFR AF: 0.983

Gnomad4 AMR AF: 0.940

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.983

Gnomad4 FIN AF: 0.911

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.938

Alfa AF: 0.918 Hom.: 34445

Bravo AF: 0.940

Asia WGS AF: 0.989 AC: 3441 AN: 3478

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

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.62
DANN	Benign	0.61

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: rs6929656; hg19: chr6-133827148;