rs10823116

Variant names:

• chr10-67923688-A-G
• rs10823116
• NM_015601.4:c.2942-549T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015601.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC4	NM_015601.4	MANE Select	c.2942-549T>C		intron	N/A	NP_056416.2
	HERC4	NM_022079.3		c.2966-549T>C		intron	N/A	NP_071362.1	Q5GLZ8-1
	HERC4	NM_001278185.2		c.2732-549T>C		intron	N/A	NP_001265114.1	Q5GLZ8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC4	ENST00000373700.9	TSL:1 MANE Select	c.2942-549T>C		intron	N/A	ENSP00000362804.4	Q5GLZ8-2
	HERC4	ENST00000395198.7	TSL:1	c.2966-549T>C		intron	N/A	ENSP00000378624.3	Q5GLZ8-1
	HERC4	ENST00000412272.6	TSL:1	c.2732-549T>C		intron	N/A	ENSP00000416504.2	Q5GLZ8-3

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

African (AFR) AF: 0.0275 AC: 1142 AN: 41492

American (AMR) AF: 0.134 AC: 2050 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 161 AN: 3466

East Asian (EAS) AF: 0.404 AC: 2082 AN: 5154

South Asian (SAS) AF: 0.129 AC: 619 AN: 4802

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10546

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4521 AN: 67990

Other (OTH) AF: 0.0779 AC: 164 AN: 2106

Alfa AF: 0.0685 Hom.: 483

Bravo AF: 0.0810

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10823116; hg19: chr10-69683445;