Genetic Variant NM_024503.5:c.7091G>A (chr1-41510581-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_024503.5(HIVEP3):c.7091G>A(p.Arg2364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,559,070 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.298

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045588017).

BP6

Variant 1-41510581-C-T is Benign according to our data. Variant chr1-41510581-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3046158.Status of the report is no_assertion_criteria_provided, 0 stars.

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.7091G>A	p.Arg2364His	missense	Exon 9 of 9	NP_078779.2	Q5T1R4-1
	HIVEP3	NM_001127714.3		c.7088G>A	p.Arg2363His	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.7091G>A	p.Arg2364His	missense	Exon 9 of 9	ENSP00000361664.1	Q5T1R4-1
HIVEP3	ENST00000372584.5	TSL:1	c.7088G>A	p.Arg2363His	missense	Exon 8 of 8	ENSP00000361665.1	Q5T1R4-2
HIVEP3	ENST00000643665.1		c.7088G>A	p.Arg2363His	missense	Exon 8 of 8	ENSP00000494598.1	Q5T1R4-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000226

AC:

AN:

163486

AF XY:

0.000253

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00283

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000155

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000476

AC:

AN:

1406790

Hom.:

Cov.:

AF XY:

0.0000504

AC XY:

AN XY:

694770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32010

American (AMR)

AF:

0.00

AC:

AN:

36728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25242

East Asian (EAS)

AF:

0.00126

AC:

AN:

36444

South Asian (SAS)

AF:

0.0000375

AC:

AN:

80008

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5072

European-Non Finnish (NFE)

AF:

0.0000111

AC:

AN:

1083848

Other (OTH)

AF:

0.0000858

AC:

AN:

58286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000131

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41564

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00270

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000194

Hom.:

Bravo

AF:

0.000162

ExAC

AF:

0.0000778

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HIVEP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.1

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.088

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.64

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

PhyloP100

0.30

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.17

REVEL

Benign

0.023

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.0030

Vest4

0.041

MVP

0.030

MPC

0.23

ClinPred

0.0040

GERP RS

-1.1

Varity_R

0.020

gMVP

0.054

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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