chr1-41510858-C-T

Variant names:

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.6814G>A(p.Gly2272Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 1,613,218 control chromosomes in the GnomAD database, including 3,544 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 1038 hom., cov: 33)

Exomes 𝑓: 0.047 ( 2506 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00200

Publications

12 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=9.978712E-4).

BP6

Variant 1-41510858-C-T is Benign according to our data. Variant chr1-41510858-C-T is described in ClinVar as Benign. ClinVar VariationId is 402942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024503.5. 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
	HIVEP3	NM_024503.5	MANE Select	c.6814G>A	p.Gly2272Arg	missense	Exon 9 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.6811G>A	p.Gly2271Arg	missense	Exon 8 of 8	NP_001121186.1	Q5T1R4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HIVEP3	ENST00000372583.6	TSL:1 MANE Select	c.6814G>A	p.Gly2272Arg	missense	Exon 9 of 9	ENSP00000361664.1	Q5T1R4-1
HIVEP3	ENST00000372584.5	TSL:1	c.6811G>A	p.Gly2271Arg	missense	Exon 8 of 8	ENSP00000361665.1	Q5T1R4-2
HIVEP3	ENST00000643665.1		c.6811G>A	p.Gly2271Arg	missense	Exon 8 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes

AF:

0.0880

AC:

13382

AN:

152112

Hom.:

1029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0590

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0419

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0398

Gnomad OTH

AF:

0.0808

GnomAD2 exomes

AF:

0.0572

AC:

14287

AN:

249762

AF XY:

0.0574

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0635

Gnomad EAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0370

Gnomad NFE exome

AF:

0.0408

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0467

AC:

68190

AN:

1460988

Hom.:

2506

Cov.:

AF XY:

0.0478

AC XY:

34765

AN XY:

726800

show subpopulations

African (AFR)

AF:

0.211

AC:

7067

AN:

33470

American (AMR)

AF:

0.0364

AC:

1629

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0641

AC:

1674

AN:

26122

East Asian (EAS)

AF:

0.0111

AC:

441

AN:

39692

South Asian (SAS)

AF:

0.0988

AC:

8524

AN:

86252

European-Finnish (FIN)

AF:

0.0376

AC:

1984

AN:

52752

Middle Eastern (MID)

AF:

0.123

AC:

708

AN:

5768

European-Non Finnish (NFE)

AF:

0.0383

AC:

42615

AN:

1111854

Other (OTH)

AF:

0.0588

AC:

3548

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3888

7776

11663

15551

19439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1754

3508

5262

7016

8770

<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:

0.0882

AC:

13427

AN:

152230

Hom.:

1038

Cov.:

AF XY:

0.0873

AC XY:

6498

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.206

AC:

8555

AN:

41508

American (AMR)

AF:

0.0453

AC:

693

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

205

AN:

3472

East Asian (EAS)

AF:

0.0174

AC:

AN:

5174

South Asian (SAS)

AF:

0.106

AC:

514

AN:

4832

European-Finnish (FIN)

AF:

0.0419

AC:

445

AN:

10622

Middle Eastern (MID)

AF:

0.116

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0399

AC:

2710

AN:

68002

Other (OTH)

AF:

0.0837

AC:

177

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

608

1216

1824

2432

3040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0526

Hom.:

1539

Bravo

AF:

0.0927

TwinsUK

AF:

0.0316

AC:

117

ALSPAC

AF:

0.0426

AC:

164

ESP6500AA

AF:

0.206

AC:

909

ESP6500EA

AF:

0.0430

AC:

370

ExAC

AF:

0.0619

AC:

7508

Asia WGS

AF:

0.0940

AC:

327

AN:

3478

EpiCase

AF:

0.0391

EpiControl

AF:

0.0401

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

HIVEP3-related disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.036

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.22

MetaRNN

Benign

0.0010

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.90

PhyloP100

0.0020

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.3

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.063

MutPred

0.044

Gain of MoRF binding (P = 0.0891)

MPC

0.22

ClinPred

0.0037

GERP RS

2.6

Varity_R

0.040

gMVP

0.026

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over