Variant rs2228210 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002114.4(HIVEP1):c.2146A>G(p.Thr716Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,794 control chromosomes in the GnomAD database, including 90,091 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 6163 hom., cov: 32)

Exomes 𝑓: 0.33 ( 83928 hom. )

Consequence

HIVEP1
NM_002114.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Variant links:

Genes affected

HIVEP1 (HGNC:4920): (HIVEP zinc finger 1) This gene encodes a transcription factor belonging to the ZAS family, members of which are large proteins that contain a ZAS domain - a modular protein structure consisting of a pair of C2H2 zinc fingers with an acidic-rich region and a serine/threonine-rich sequence. These proteins bind specifically to the DNA sequence motif, GGGACTTTCC, found in the enhancer elements of several viral promoters, including human immunodeficiency virus (HIV), and to related sequences found in the enhancer elements of a number of cellular promoters. This protein binds to this sequence motif, suggesting a role in the transcriptional regulation of both viral and cellular genes. [provided by RefSeq, Oct 2011]

HIVEP1 links:

HIVEP1 (HGNC:):

HIVEP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003978461).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIVEP1	NM_002114.4 linkuse as main transcript	c.2146A>G	p.Thr716Ala	missense_variant	4/9	ENST00000379388.7	NP_002105.3	P15822-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HIVEP1	ENST00000379388.7 linkuse as main transcript	c.2146A>G	p.Thr716Ala	missense_variant	4/9	1	NM_002114.4	ENSP00000368698.2	P15822-1
HIVEP1	ENST00000541134.5 linkuse as main transcript	c.2146A>G	p.Thr716Ala	missense_variant	4/9	5			F5H212
HIVEP1	ENST00000627968 linkuse as main transcript	c.-4158A>G		5_prime_UTR_variant	4/8	5		ENSP00000486543.2	A0A0D9SFF3
HIVEP1	ENST00000442081.6 linkuse as main transcript	c.166+2007A>G		intron_variant		3		ENSP00000409078.3	C9JLG1

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39066

AN:

151946

Hom.:

6171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0678

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.350

Gnomad OTH

AF:

0.277

GnomAD3 exomes

AF:

0.301

AC:

74911

AN:

248896

Hom.:

12260

AF XY:

0.307

AC XY:

41541

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.0609

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.233

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.348

Gnomad NFE exome

AF:

0.357

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.334

AC:

488143

AN:

1461730

Hom.:

83928

Cov.:

AF XY:

0.333

AC XY:

242491

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0560

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.353

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.354

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.257

AC:

39045

AN:

152064

Hom.:

6163

Cov.:

AF XY:

0.254

AC XY:

18878

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0677

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.350

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.336

Hom.:

23073

Bravo

AF:

0.248

TwinsUK

AF:

0.361

AC:

1340

ALSPAC

AF:

0.347

AC:

1336

ESP6500AA

AF:

0.0657

AC:

274

ESP6500EA

AF:

0.350

AC:

2940

ExAC

AF:

0.299

AC:

36244

Asia WGS

AF:

0.253

AC:

877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.060

DANN

Benign

0.31

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.34

T;.

MetaRNN

Benign

0.0040

T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.90

.;N

REVEL

Benign

0.027

Sift

Benign

0.36

.;T

Sift4G

Benign

0.50

T;T

Vest4

0.015

MPC

0.084

ClinPred

0.013

GERP RS

-7.6

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over