1-41510704-C-T

Position:

chr1-41510704-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_024503.5(HIVEP3):c.6968G>A(p.Arg2323Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00749 in 1,526,540 control chromosomes in the GnomAD database, including 164 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 (no stars).

Frequency

Genomes: 𝑓 0.0056 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 154 hom. )

Consequence

HIVEP3
NM_024503.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.00400

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=0.0020682514).

BP6

Variant 1-41510704-C-T is Benign according to our data. Variant chr1-41510704-C-T is described in ClinVar as [Benign]. Clinvar id is 3042394.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00561 (854/152276) while in subpopulation SAS AF= 0.0464 (224/4826). AF 95% confidence interval is 0.0414. There are 10 homozygotes in gnomad4. There are 476 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP3	NM_024503.5 linkuse as main transcript	c.6968G>A	p.Arg2323Gln	missense_variant	9/9	ENST00000372583.6
HIVEP3	NM_001127714.3 linkuse as main transcript	c.6965G>A	p.Arg2322Gln	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP3	ENST00000372583.6 linkuse as main transcript	c.6968G>A	p.Arg2323Gln	missense_variant	9/9	1	NM_024503.5	P5	Q5T1R4-1
HIVEP3	ENST00000372584.5 linkuse as main transcript	c.6965G>A	p.Arg2322Gln	missense_variant	8/8	1		A2	Q5T1R4-2
HIVEP3	ENST00000643665.1 linkuse as main transcript	c.6965G>A	p.Arg2322Gln	missense_variant	8/8			A2	Q5T1R4-2
HIVEP3	ENST00000460604.1 linkuse as main transcript	n.1895G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00562

AC:

855

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0462

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.0100

AC:

1395

AN:

138950

Hom.:

AF XY:

0.0126

AC XY:

947

AN XY:

75366

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00831

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.00282

Gnomad NFE exome

AF:

0.00666

Gnomad OTH exome

AF:

0.0117

GnomAD4 exome

AF:

0.00770

AC:

10587

AN:

1374264

Hom.:

154

Cov.:

AF XY:

0.00885

AC XY:

5973

AN XY:

674976

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00825

Gnomad4 EAS exome

AF:

0.0000823

Gnomad4 SAS exome

AF:

0.0436

Gnomad4 FIN exome

AF:

0.00205

Gnomad4 NFE exome

AF:

0.00589

Gnomad4 OTH exome

AF:

0.00769

GnomAD4 genome

AF:

0.00561

AC:

854

AN:

152276

Hom.:

Cov.:

AF XY:

0.00639

AC XY:

476

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0464

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00612

Hom.:

Bravo

AF:

0.00454

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000765

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00749

AC:

856

Asia WGS

AF:

0.0120

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

Feb 21, 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

0.069

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

DANN

Uncertain

0.98

DEOGEN2

Benign

0.046

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.60

.;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.64

.;N;N

REVEL

Benign

0.034

Sift

Benign

0.42

.;T;T

Sift4G

Benign

0.54

.;T;T

Polyphen

0.0030

B;B;B

Vest4

0.080, 0.063

MPC

0.21

ClinPred

0.0065

GERP RS

0.15

Varity_R

0.028

gMVP

0.037

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