rs10823116

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015601.4(HERC4):​c.2942-549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,022 control chromosomes in the GnomAD database, including 1,006 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 0.084 ( 1006 hom., cov: 32)

Consequence

HERC4
NM_015601.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HERC4NM_015601.4 linkuse as main transcriptc.2942-549T>C intron_variant ENST00000373700.9 NP_056416.2 Q5GLZ8-2A0A024QZN8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HERC4ENST00000373700.9 linkuse as main transcriptc.2942-549T>C intron_variant 1 NM_015601.4 ENSP00000362804.4 Q5GLZ8-2

Frequencies

GnomAD3 genomes
AF:
0.0845
AC:
12840
AN:
151904
Hom.:
1004
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0276
Gnomad AMI
AF:
0.0746
Gnomad AMR
AF:
0.134
Gnomad ASJ
AF:
0.0465
Gnomad EAS
AF:
0.403
Gnomad SAS
AF:
0.131
Gnomad FIN
AF:
0.189
Gnomad MID
AF:
0.108
Gnomad NFE
AF:
0.0665
Gnomad OTH
AF:
0.0792
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0844
AC:
12838
AN:
152022
Hom.:
1006
Cov.:
32
AF XY:
0.0927
AC XY:
6884
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.0275
Gnomad4 AMR
AF:
0.134
Gnomad4 ASJ
AF:
0.0465
Gnomad4 EAS
AF:
0.404
Gnomad4 SAS
AF:
0.129
Gnomad4 FIN
AF:
0.189
Gnomad4 NFE
AF:
0.0665
Gnomad4 OTH
AF:
0.0779
Alfa
AF:
0.0684
Hom.:
349
Bravo
AF:
0.0810
Asia WGS
AF:
0.227
AC:
790
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
5.5
DANN
Benign
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10823116; hg19: chr10-69683445; API