rs866255
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_015601.4(HERC4):c.1011C>T(p.Ser337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,611,320 control chromosomes in the GnomAD database, including 119,154 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 0.38 ( 12108 hom., cov: 31)
Exomes 𝑓: 0.37 ( 107046 hom. )
Consequence
HERC4
NM_015601.4 synonymous
NM_015601.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.48
Genes affected
HERC4 (HGNC:24521): (HECT and RLD domain containing E3 ubiquitin protein ligase 4) HERC4 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP7
?
Synonymous conserved (PhyloP=1.48 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HERC4 | NM_015601.4 | c.1011C>T | p.Ser337= | synonymous_variant | 9/25 | ENST00000373700.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC4 | ENST00000373700.9 | c.1011C>T | p.Ser337= | synonymous_variant | 9/25 | 1 | NM_015601.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.385 AC: 58410AN: 151744Hom.: 12089 Cov.: 31
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GnomAD3 exomes AF: 0.437 AC: 109631AN: 250934Hom.: 27173 AF XY: 0.434 AC XY: 58827AN XY: 135634
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GnomAD4 exome AF: 0.368 AC: 536718AN: 1459458Hom.: 107046 Cov.: 33 AF XY: 0.372 AC XY: 269877AN XY: 726168
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GnomAD4 genome ? AF: 0.385 AC: 58466AN: 151862Hom.: 12108 Cov.: 31 AF XY: 0.393 AC XY: 29175AN XY: 74232
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at