Variant 4-88463979-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016323.4(HERC5):c.905G>C(p.Cys302Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00336 in 1,612,714 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 135 hom. )

Consequence

HERC5
NM_016323.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.04

Variant links:

Genes affected

HERC5 (HGNC:24368): (HECT and RLD domain containing E3 ubiquitin protein ligase 5) This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and perinuclear region and functions as an interferon-induced E3 protein ligase that mediates ISGylation of protein targets. The protein also acts as a modulator of the antiviral immune response. The gene lies in a cluster of HERC family genes on chromosome 4. [provided by RefSeq, Aug 2021]

HERC5 links:

LOC102723458 (HGNC:):

LOC102723458 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015646249).

BP6

Variant 4-88463979-G-C is Benign according to our data. Variant chr4-88463979-G-C is described in ClinVar as [Benign]. Clinvar id is 789471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HERC5	NM_016323.4 linkuse as main transcript	c.905G>C	p.Cys302Ser	missense_variant	6/23	ENST00000264350.8
HERC5	XM_011532022.3 linkuse as main transcript	c.905G>C	p.Cys302Ser	missense_variant	6/21
LOC102723458	XR_938972.3 linkuse as main transcript	n.19+3652C>G		intron_variant, non_coding_transcript_variant
LOC102723458	XR_938976.3 linkuse as main transcript	n.76+3652C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HERC5	ENST00000264350.8 linkuse as main transcript	c.905G>C	p.Cys302Ser	missense_variant	6/23	1	NM_016323.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

576

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.0471

Gnomad SAS

AF:

0.00229

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.00805

AC:

2019

AN:

250814

Hom.:

AF XY:

0.00690

AC XY:

935

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.00466

Gnomad EAS exome

AF:

0.0452

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.00524

GnomAD4 exome

AF:

0.00332

AC:

4847

AN:

1460716

Hom.:

135

Cov.:

AF XY:

0.00317

AC XY:

2307

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0301

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.0673

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000290

Gnomad4 OTH exome

AF:

0.00388

GnomAD4 genome

AF:

0.00377

AC:

573

AN:

151998

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.0152

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.0472

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00268

Hom.:

Bravo

AF:

0.00551

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00714

AC:

867

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.56

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-9.5

REVEL

Pathogenic

0.82

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.89

MutPred

0.85

Gain of MoRF binding (P = 0.0746);

MVP

0.99

MPC

0.69

ClinPred

0.11

GERP RS

4.8

Varity_R

0.92

gMVP

0.86

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over