chr6-133462487-ATCT-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_004100.5(EYA4):c.580+14_580+16delTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,613,946 control chromosomes in the GnomAD database, including 725 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004100.5 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0335 AC: 5090AN: 152138Hom.: 238 Cov.: 32
GnomAD3 exomes AF: 0.0198 AC: 4961AN: 251064Hom.: 212 AF XY: 0.0195 AC XY: 2642AN XY: 135674
GnomAD4 exome AF: 0.00825 AC: 12054AN: 1461690Hom.: 485 AF XY: 0.00916 AC XY: 6663AN XY: 727144
GnomAD4 genome AF: 0.0335 AC: 5096AN: 152256Hom.: 240 Cov.: 32 AF XY: 0.0339 AC XY: 2526AN XY: 74436
ClinVar
Submissions by phenotype
not specified Benign:3
c.580+14_580+16delTCT in intron 8 of EYA4: This variant is not expected to have clinical significance because it has been identified in 10.3% (53/1072) of Afric an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs139659489) -
- -
Variant summary: EYA4 c.580+14_580+16delTCT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.02 in 251064 control chromosomes, predominantly at a frequency of 0.1 within the African or African-American subpopulation in the gnomAD database, including 90 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4000-folds over the estimated maximal expected allele frequency for a pathogenic variant in EYA4 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Co-occurrence with another likely pathogenic TTN variant (c.34782_34785delTTGT, p.C11595fsX9) has been reported in an internal sample, providing supporting evidence for a benign role. Two ClinVar submissions (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign. -
Nonsyndromic Hearing Loss, Dominant Benign:1
- -
Dilated Cardiomyopathy, Dominant Benign:1
- -
not provided Benign:1
- -
Dilated cardiomyopathy 1J Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at