chr1-41510657-T-C

Position:

chr1-41510657-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024503.5(HIVEP3):c.7015A>G(p.Thr2339Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,533,770 control chromosomes in the GnomAD database, including 757,851 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.97 ( 71866 hom., cov: 32)

Exomes 𝑓: 1.0 ( 685985 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.588

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=1.3137944E-6).

BP6

Variant 1-41510657-T-C is Benign according to our data. Variant chr1-41510657-T-C is described in ClinVar as [Benign]. Clinvar id is 402941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 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.7015A>G	p.Thr2339Ala	missense_variant	9/9	ENST00000372583.6	NP_078779.2
HIVEP3	NM_001127714.3 linkuse as main transcript	c.7012A>G	p.Thr2338Ala	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.7015A>G	p.Thr2339Ala	missense_variant	9/9	1	NM_024503.5	ENSP00000361664	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.7012A>G	p.Thr2338Ala	missense_variant	8/8	1		ENSP00000361665	A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.7012A>G	p.Thr2338Ala	missense_variant	8/8			ENSP00000494598	A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1942A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.971

AC:

147672

AN:

152118

Hom.:

71818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.988

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.978

GnomAD3 exomes

AF:

0.993

AC:

139881

AN:

140928

Hom.:

69458

AF XY:

0.994

AC XY:

75168

AN XY:

75604

show subpopulations

Gnomad AFR exome

AF:

0.890

Gnomad AMR exome

AF:

0.994

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.993

GnomAD4 exome

AF:

0.996

AC:

1376544

AN:

1381534

Hom.:

685985

Cov.:

AF XY:

0.997

AC XY:

677562

AN XY:

679732

show subpopulations

Gnomad4 AFR exome

AF:

0.892

Gnomad4 AMR exome

AF:

0.993

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.999

Gnomad4 OTH exome

AF:

0.991

GnomAD4 genome

AF:

0.971

AC:

147778

AN:

152236

Hom.:

71866

Cov.:

AF XY:

0.972

AC XY:

72340

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.901

Gnomad4 AMR

AF:

0.988

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.978

Alfa

AF:

0.987

Hom.:

13008

Bravo

AF:

0.967

TwinsUK

AF:

0.999

AC:

3705

ALSPAC

AF:

0.999

AC:

3849

ESP6500AA

AF:

0.915

AC:

3684

ESP6500EA

AF:

0.997

AC:

7782

ExAC

AF:

0.981

AC:

87682

Asia WGS

AF:

0.991

AC:

3446

AN:

3478

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: Frequency -

HIVEP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 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

0.051

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.22

DANN

Benign

0.13

DEOGEN2

Benign

0.053

.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.18

.;T;T

MetaRNN

Benign

0.0000013

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.63

.;N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.40

PROVEAN

Benign

0.17

.;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

.;T;T

Sift4G

Benign

1.0

.;T;T

Polyphen

0.0

B;B;B

Vest4

0.022, 0.015

MPC

0.18

ClinPred

0.00068

GERP RS

2.2

Varity_R

0.027

gMVP

0.043

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