rs72669005

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024503.5(HIVEP3):c.7126C>T(p.Pro2376Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0559 in 1,576,608 control chromosomes in the GnomAD database, including 3,656 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 913 hom., cov: 33)

Exomes 𝑓: 0.053 ( 2743 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.17

Publications

10 publications found

Variant links:

Genes affected

HIVEP3 (HGNC:13561): (HIVEP zinc finger 3) This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Sep 2011]

HIVEP3 links:

ENSG00000295052 (HGNC:):

ENSG00000295052 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012972653).

BP6

Variant 1-41510546-G-A is Benign according to our data. Variant chr1-41510546-G-A is described in ClinVar as Benign. ClinVar VariationId is 402940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5 link	c.7126C>T	p.Pro2376Ser	missense_variant	Exon 9 of 9	ENST00000372583.6	NP_078779.2	Q5T1R4-1
HIVEP3	NM_001127714.3 link	c.7123C>T	p.Pro2375Ser	missense_variant	Exon 8 of 8		NP_001121186.1	Q5T1R4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6 link	c.7126C>T	p.Pro2376Ser	missense_variant	Exon 9 of 9	1	NM_024503.5	ENSP00000361664.1		Q5T1R4-1

Frequencies

GnomAD3 genomes

AF:

0.0859

AC:

13063

AN:

152078

Hom.:

907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0522

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0369

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0452

Gnomad OTH

AF:

0.0766

GnomAD2 exomes

AF:

0.0659

AC:

12199

AN:

185134

AF XY:

0.0671

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0659

Gnomad ASJ exome

AF:

0.0557

Gnomad EAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.0356

Gnomad NFE exome

AF:

0.0489

Gnomad OTH exome

AF:

0.0589

GnomAD4 exome

AF:

0.0527

AC:

75009

AN:

1424412

Hom.:

2743

Cov.:

AF XY:

0.0539

AC XY:

38023

AN XY:

704980

show subpopulations

African (AFR)

AF:

0.197

AC:

6432

AN:

32662

American (AMR)

AF:

0.0641

AC:

2527

AN:

39444

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

1422

AN:

25422

East Asian (EAS)

AF:

0.00365

AC:

138

AN:

37818

South Asian (SAS)

AF:

0.114

AC:

9266

AN:

81194

European-Finnish (FIN)

AF:

0.0366

AC:

1849

AN:

50554

Middle Eastern (MID)

AF:

0.118

AC:

615

AN:

5226

European-Non Finnish (NFE)

AF:

0.0450

AC:

49157

AN:

1093184

Other (OTH)

AF:

0.0612

AC:

3603

AN:

58908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

3905

7810

11714

15619

19524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2028

4056

6084

8112

10140

<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:

0.0861

AC:

13100

AN:

152196

Hom.:

913

Cov.:

AF XY:

0.0851

AC XY:

6332

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.188

AC:

7794

AN:

41510

American (AMR)

AF:

0.0582

AC:

891

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0522

AC:

181

AN:

3468

East Asian (EAS)

AF:

0.00252

AC:

AN:

5164

South Asian (SAS)

AF:

0.114

AC:

552

AN:

4824

European-Finnish (FIN)

AF:

0.0369

AC:

392

AN:

10616

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0452

AC:

3076

AN:

67992

Other (OTH)

AF:

0.0777

AC:

164

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

598

1196

1794

2392

2990

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0516

Hom.:

177

Bravo

AF:

0.0916

TwinsUK

AF:

0.0361

AC:

134

ALSPAC

AF:

0.0480

AC:

185

ESP6500AA

AF:

0.180

AC:

790

ESP6500EA

AF:

0.0496

AC:

426

ExAC

AF:

0.0574

AC:

6830

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

HIVEP3-related disorder

Benign:1

Apr 05, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

.;T;.

Eigen

Benign

0.044

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

.;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

.;L;.

PhyloP100

2.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

.;N;N

REVEL

Benign

0.027

Sift

Benign

0.050

.;D;T

Sift4G

Benign

0.077

.;T;T

Polyphen

0.87

P;P;P

Vest4

0.073, 0.13

MPC

0.30

ClinPred

0.012

GERP RS

4.3

Varity_R

0.092

gMVP

0.085

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over