rs10823116

Positions:

• chr10-67923688-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ACMG classification

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
HERC4	NM_015601.4	c.2942-549T>C		intron_variant		ENST00000373700.9	NP_056416.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC4	ENST00000373700.9	c.2942-549T>C		intron_variant		1	NM_015601.4	ENSP00000362804.4

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12840 AN: 151904 Hom.: 1004 Cov.: 32

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

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

Other links and lift over

dbSNP: rs10823116; hg19: chr10-69683445;