rs16924989
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_015601.4(HERC4):c.2337+333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 175,894 control chromosomes in the GnomAD database, including 1,167 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 ( 971 hom., cov: 32)
Exomes 𝑓: 0.12 ( 196 hom. )
Consequence
HERC4
NM_015601.4 intron
NM_015601.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.91
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HERC4 | NM_015601.4 | c.2337+333T>C | intron_variant | ENST00000373700.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HERC4 | ENST00000373700.9 | c.2337+333T>C | intron_variant | 1 | NM_015601.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.111 AC: 16849AN: 152084Hom.: 971 Cov.: 32
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GnomAD4 exome AF: 0.119 AC: 2826AN: 23692Hom.: 196 Cov.: 0 AF XY: 0.119 AC XY: 1471AN XY: 12330
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GnomAD4 genome ? AF: 0.111 AC: 16864AN: 152202Hom.: 971 Cov.: 32 AF XY: 0.111 AC XY: 8247AN XY: 74410
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at