dbSNP rs16924989: HERC4:c.2337+333T>C (chr10-67954262-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015601.4(HERC4):c.2337+333T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 175,894 control chromosomes in the GnomAD database, including 1,167 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 0.11 ( 971 hom., cov: 32)

Exomes 𝑓: 0.12 ( 196 hom. )

Consequence

HERC4
NM_015601.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.91

Publications

1 publications found

Variant links:

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]

HERC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERC4	NM_015601.4 link	c.2337+333T>C		intron_variant	Intron 19 of 24	ENST00000373700.9	NP_056416.2	Q5GLZ8-2A0A024QZN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERC4	ENST00000373700.9 link	c.2337+333T>C		intron_variant	Intron 19 of 24	1	NM_015601.4	ENSP00000362804.4		Q5GLZ8-2

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16849

AN:

152084

Hom.:

971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0737

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0995

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.119

AC:

2826

AN:

23692

Hom.:

196

Cov.:

AF XY:

0.119

AC XY:

1471

AN XY:

12330

show subpopulations

African (AFR)

AF:

0.0699

AC:

AN:

916

American (AMR)

AF:

0.136

AC:

122

AN:

898

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

112

AN:

984

East Asian (EAS)

AF:

0.120

AC:

182

AN:

1520

South Asian (SAS)

AF:

0.134

AC:

AN:

674

European-Finnish (FIN)

AF:

0.0833

AC:

AN:

816

Middle Eastern (MID)

AF:

0.0625

AC:

AN:

European-Non Finnish (NFE)

AF:

0.123

AC:

1986

AN:

16202

Other (OTH)

AF:

0.124

AC:

196

AN:

1586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

125

251

376

502

627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.111

AC:

16864

AN:

152202

Hom.:

971

Cov.:

AF XY:

0.111

AC XY:

8247

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0737

AC:

3063

AN:

41550

American (AMR)

AF:

0.140

AC:

2142

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

468

AN:

3470

East Asian (EAS)

AF:

0.130

AC:

676

AN:

5188

South Asian (SAS)

AF:

0.147

AC:

708

AN:

4822

European-Finnish (FIN)

AF:

0.0995

AC:

1054

AN:

10592

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8430

AN:

67978

Other (OTH)

AF:

0.117

AC:

247

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

762

1524

2285

3047

3809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

171

Bravo

AF:

0.110

Asia WGS

AF:

0.127

AC:

442

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.7

(source)

DANN

Benign

0.78

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over