chr1-41583469-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024503.5(HIVEP3):c.1329G>C(p.Leu443Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.992 in 1,613,904 control chromosomes in the GnomAD database, including 794,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70069 hom., cov: 29)

Exomes 𝑓: 1.0 ( 724922 hom. )

Consequence

HIVEP3
NM_024503.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.334

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 1-41583469-C-G is Benign according to our data. Variant chr1-41583469-C-G is described in ClinVar as Benign. ClinVar VariationId is 402947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.334 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIVEP3	NM_024503.5 link	c.1329G>C	p.Leu443Leu	synonymous_variant	Exon 4 of 9	ENST00000372583.6	NP_078779.2	Q5T1R4-1
HIVEP3	NM_001127714.3 link	c.1329G>C	p.Leu443Leu	synonymous_variant	Exon 3 of 8		NP_001121186.1	Q5T1R4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HIVEP3	ENST00000372583.6 link	c.1329G>C	p.Leu443Leu	synonymous_variant	Exon 4 of 9	1	NM_024503.5	ENSP00000361664.1	Q5T1R4-1
HIVEP3	ENST00000372584.5 link	c.1329G>C	p.Leu443Leu	synonymous_variant	Exon 3 of 8	1		ENSP00000361665.1	Q5T1R4-2
HIVEP3	ENST00000643665.1 link	c.1329G>C	p.Leu443Leu	synonymous_variant	Exon 3 of 8			ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes

AF:

0.958

AC:

145543

AN:

151974

Hom.:

70027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.852

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.986

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.968

GnomAD2 exomes

AF:

0.989

AC:

248540

AN:

251232

AF XY:

0.992

show subpopulations

Gnomad AFR exome

AF:

0.852

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.996

GnomAD4 exome

AF:

0.996

AC:

1455388

AN:

1461812

Hom.:

724922

Cov.:

AF XY:

0.996

AC XY:

724426

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.842

AC:

28192

AN:

33478

American (AMR)

AF:

0.993

AC:

44391

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26134

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39698

South Asian (SAS)

AF:

1.00

AC:

86233

AN:

86254

European-Finnish (FIN)

AF:

1.00

AC:

53402

AN:

53402

Middle Eastern (MID)

AF:

0.992

AC:

5717

AN:

5766

European-Non Finnish (NFE)

AF:

1.00

AC:

1111809

AN:

1111970

Other (OTH)

AF:

0.990

AC:

59812

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

366

732

1097

1463

1829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21666

43332

64998

86664

108330

<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:

0.958

AC:

145642

AN:

152092

Hom.:

70069

Cov.:

AF XY:

0.958

AC XY:

71222

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.852

AC:

35332

AN:

41470

American (AMR)

AF:

0.986

AC:

15078

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5144

AN:

5144

South Asian (SAS)

AF:

0.999

AC:

4789

AN:

4792

European-Finnish (FIN)

AF:

1.00

AC:

10606

AN:

10606

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

1.00

AC:

67970

AN:

68000

Other (OTH)

AF:

0.969

AC:

2046

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

266

532

797

1063

1329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.937

Hom.:

22860

Bravo

AF:

0.952

Asia WGS

AF:

0.990

AC:

3442

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

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: Frequency -

HIVEP3-related disorder

Benign:1

Oct 28, 2019

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

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.4

(source)

DANN

Benign

0.72

PhyloP100

0.33

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