4-88554608-G-C

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

HERC3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HERC3	NM_001375482.1	c.-88+30676G>C		intron_variant
HERC3	NM_001375483.1	c.-226+30676G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.278

Gnomad4 SAS AF: 0.0646

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0463

Gnomad4 OTH AF: 0.0639

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.68
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10516811; hg19: chr4-89475759;