Variant 1-41510950-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_024503.5(HIVEP3):c.6722G>A(p.Arg2241Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,613,586 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 12 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.459

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00291574).

BP6

Variant 1-41510950-C-T is Benign according to our data. Variant chr1-41510950-C-T is described in ClinVar as [Benign]. Clinvar id is 3039451.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.6722G>A	p.Arg2241Gln	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6719G>A	p.Arg2240Gln	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.6722G>A	p.Arg2241Gln	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6719G>A	p.Arg2240Gln	missense_variant	8/8	1		ENSP00000361665	A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6719G>A	p.Arg2240Gln	missense_variant	8/8			ENSP00000494598	A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1649G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

337

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00246

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00222

AC:

554

AN:

249834

Hom.:

AF XY:

0.00218

AC XY:

295

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.000874

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00146

AC:

2130

AN:

1461280

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

1122

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.00952

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00221

AC:

337

AN:

152306

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00201

Hom.:

Bravo

AF:

0.00111

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00218

AC:

265

EpiCase

AF:

0.00164

EpiControl

AF:

0.00119

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

May 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

0.076

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.093

.;T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;.

MutationTaster

Benign

0.93

N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.43

.;N;N

REVEL

Benign

0.026

Sift

Pathogenic

0.0

.;D;D

Sift4G

Benign

0.12

.;T;T

Polyphen

0.012

B;B;B

Vest4

0.082, 0.096

MVP

0.20

MPC

0.22

ClinPred

0.060

GERP RS

3.3

Varity_R

0.12

gMVP

0.18

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