4-88554608-G-C

Variant names:

• chr4-88554608-G-C
• rs10516811
• ENST00000512194.2:c.-226+30676G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375482.1(HERC3):​c.-88+30676G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 152,172 control chromosomes in the GnomAD database, including 626 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 0.076 (626 hom., cov: 32)
• Consequence: HERC3 NM_001375482.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 1 publications found

Genes affected

HERC3 (HGNC:4876): (HECT and RLD domain containing E3 ubiquitin protein ligase 3) This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375482.1. 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
	HERC3	NM_001375482.1		c.-88+30676G>C		intron	N/A	NP_001362411.1	H0Y8G9
	HERC3	NM_001375483.1		c.-226+30676G>C		intron	N/A	NP_001362412.1	H0Y8G9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HERC3	ENST00000512194.2	TSL:5	c.-226+30676G>C		intron	N/A	ENSP00000421021.2	H0Y8G9

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11557 AN: 152054 Hom.: 626 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0760 AC: 11567 AN: 152172 Hom.: 626 Cov.: 32 AF XY: 0.0778 AC XY: 5788 AN XY: 74398

African (AFR) AF: 0.119 AC: 4957 AN: 41508

American (AMR) AF: 0.0526 AC: 804 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1439 AN: 5170

South Asian (SAS) AF: 0.0646 AC: 312 AN: 4828

European-Finnish (FIN) AF: 0.0551 AC: 583 AN: 10588

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0463 AC: 3149 AN: 68016

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0193 Hom.: 11

Bravo AF: 0.0786

Asia WGS AF: 0.168 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.65
PhyloP100		0.020

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10516811; hg19: chr4-89475759;