1-41510674-T-C

Position:

chr1-41510674-T-C

Variant summary

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

The NM_024503.5(HIVEP3):c.6998A>G(p.Glu2333Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,523,114 control chromosomes in the GnomAD database, including 1,227 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 0.029 ( 96 hom., cov: 33)

Exomes 𝑓: 0.034 ( 1131 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.607

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=0.0017419457).

BP6

Variant 1-41510674-T-C is Benign according to our data. Variant chr1-41510674-T-C is described in ClinVar as [Benign]. Clinvar id is 3056543.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.094 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.6998A>G	p.Glu2333Gly	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6995A>G	p.Glu2332Gly	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.6998A>G	p.Glu2333Gly	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6995A>G	p.Glu2332Gly	missense_variant	8/8	1		ENSP00000361665	A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6995A>G	p.Glu2332Gly	missense_variant	8/8			ENSP00000494598	A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1925A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4470

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0195

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0525

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0417

AC:

5437

AN:

130418

Hom.:

183

AF XY:

0.0447

AC XY:

3137

AN XY:

70134

show subpopulations

Gnomad AFR exome

AF:

0.0168

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.0561

Gnomad EAS exome

AF:

0.00243

Gnomad SAS exome

AF:

0.0948

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0429

GnomAD4 exome

AF:

0.0344

AC:

47141

AN:

1370890

Hom.:

1131

Cov.:

AF XY:

0.0360

AC XY:

24228

AN XY:

672988

show subpopulations

Gnomad4 AFR exome

AF:

0.0205

Gnomad4 AMR exome

AF:

0.0517

Gnomad4 ASJ exome

AF:

0.0572

Gnomad4 EAS exome

AF:

0.00375

Gnomad4 SAS exome

AF:

0.0941

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.0305

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0294

AC:

4472

AN:

152224

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

2176

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.0378

Gnomad4 ASJ

AF:

0.0525

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0384

Alfa

AF:

0.0338

Hom.:

Bravo

AF:

0.0300

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0322

AC:

124

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.0228

AC:

176

ExAC

AF:

0.0227

AC:

2466

Asia WGS

AF:

0.0700

AC:

245

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

Nov 16, 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

0.077

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.085

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.57

.;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.63

.;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.31

.;N;N

REVEL

Benign

0.016

Sift

Benign

0.093

.;T;T

Sift4G

Benign

0.38

.;T;T

Polyphen

0.0010

B;B;B

Vest4

0.076, 0.080

MPC

0.22

ClinPred

0.00022

GERP RS

1.3

Varity_R

0.037

gMVP

0.092

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