Variant 1-41510659-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_024503.5(HIVEP3):c.7013C>T(p.Pro2338Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00504 in 1,526,972 control chromosomes in the GnomAD database, including 330 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.026 ( 183 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 147 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.188

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024409592).

BP6

Variant 1-41510659-G-A is Benign according to our data. Variant chr1-41510659-G-A is described in ClinVar as [Benign]. Clinvar id is 3037301.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.7013C>T	p.Pro2338Leu	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3 linkuse as main transcript	c.7010C>T	p.Pro2337Leu	missense_variant	8/8		NP_001121186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP3	ENST00000372583.6 linkuse as main transcript	c.7013C>T	p.Pro2338Leu	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.7010C>T	p.Pro2337Leu	missense_variant	8/8	1		ENSP00000361665	A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.7010C>T	p.Pro2337Leu	missense_variant	8/8			ENSP00000494598	A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1940C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

3956

AN:

152162

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0904

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.00618

AC:

834

AN:

135002

Hom.:

AF XY:

0.00505

AC XY:

366

AN XY:

72510

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000366

Gnomad SAS exome

AF:

0.000623

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.00205

GnomAD4 exome

AF:

0.00272

AC:

3737

AN:

1374692

Hom.:

147

Cov.:

AF XY:

0.00238

AC XY:

1608

AN XY:

675394

show subpopulations

Gnomad4 AFR exome

AF:

0.0958

Gnomad4 AMR exome

AF:

0.00384

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000197

Gnomad4 SAS exome

AF:

0.000710

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000223

Gnomad4 OTH exome

AF:

0.00543

GnomAD4 genome

AF:

0.0260

AC:

3961

AN:

152280

Hom.:

183

Cov.:

AF XY:

0.0257

AC XY:

1914

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0902

Gnomad4 AMR

AF:

0.00928

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.0300

ESP6500AA

AF:

0.0679

AC:

273

ESP6500EA

AF:

0.000644

AC:

ExAC

AF:

0.00638

AC:

664

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HIVEP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 2019

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.020

DANN

Benign

0.42

DEOGEN2

Benign

0.077

.;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.57

.;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.46

.;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.79

.;N;N

REVEL

Benign

0.032

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.42

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.032, 0.043

MVP

0.055

MPC

0.19

ClinPred

0.0014

GERP RS

-5.5

Varity_R

0.025

gMVP

0.028

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over