1-41510858-C-T

Position:

chr1-41510858-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.6814G>A	p.Gly2272Arg	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6811G>A	p.Gly2271Arg	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.6814G>A	p.Gly2272Arg	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6811G>A	p.Gly2271Arg	missense_variant	8/8	1		ENSP00000361665	A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6811G>A	p.Gly2271Arg	missense_variant	8/8			ENSP00000494598	A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1741G>A		non_coding_transcript_exon_variant	5/5	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

GnomAD3 exomes

AF:

0.0572

AC:

14287

AN:

249762

Hom.:

684

AF XY:

0.0574

AC XY:

7776

AN XY:

135548

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 SAS exome

AF:

0.101

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

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.0364

Gnomad4 ASJ exome

AF:

0.0641

Gnomad4 EAS exome

AF:

0.0111

Gnomad4 SAS exome

AF:

0.0988

Gnomad4 FIN exome

AF:

0.0376

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0588

GnomAD4 genome

AF:

0.0882

AC:

13427

AN:

152230

Hom.:

1038

Cov.:

AF XY:

0.0873

AC XY:

6498

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.206

Gnomad4 AMR

AF:

0.0453

Gnomad4 ASJ

AF:

0.0590

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.0419

Gnomad4 NFE

AF:

0.0399

Gnomad4 OTH

AF:

0.0837

Alfa

AF:

0.0458

Hom.:

537

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 13, 2021

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.17

DEOGEN2

Benign

0.036

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.22

.;T;T

MetaRNN

Benign

0.0010

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.90

.;N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.3

.;N;N

REVEL

Benign

0.028

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.62

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.063, 0.058

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

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