Variant rs2228213 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.4827G>A(p.Met1609Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,613,710 control chromosomes in the GnomAD database, including 87,650 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 ( 6157 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81493 hom. )

Consequence

HIVEP1
NM_002114.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.614

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:

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=0.004592508).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIVEP1	NM_002114.4 linkuse as main transcript	c.4827G>A	p.Met1609Ile	missense_variant	4/9	ENST00000379388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIVEP1	ENST00000379388.7 linkuse as main transcript	c.4827G>A	p.Met1609Ile	missense_variant	4/9	1	NM_002114.4	P2	P15822-1
HIVEP1	ENST00000541134.5 linkuse as main transcript	c.4827G>A	p.Met1609Ile	missense_variant	4/9	5		A2
HIVEP1	ENST00000627968.2 linkuse as main transcript	c.-1477G>A		5_prime_UTR_variant	4/8	5
HIVEP1	ENST00000442081.6 linkuse as main transcript	c.166+4688G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39975

AN:

151990

Hom.:

6165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0962

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.281

GnomAD3 exomes

AF:

0.300

AC:

74761

AN:

249464

Hom.:

12109

AF XY:

0.305

AC XY:

41329

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.0898

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.330

AC:

481654

AN:

1461602

Hom.:

81493

Cov.:

AF XY:

0.329

AC XY:

239101

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.348

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.263

AC:

39963

AN:

152108

Hom.:

6157

Cov.:

AF XY:

0.260

AC XY:

19337

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0961

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.331

Hom.:

20114

Bravo

AF:

0.255

TwinsUK

AF:

0.356

AC:

1321

ALSPAC

AF:

0.342

AC:

1319

ESP6500AA

AF:

0.0912

AC:

375

ESP6500EA

AF:

0.343

AC:

2879

ExAC

AF:

0.299

AC:

36126

Asia WGS

AF:

0.250

AC:

869

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.26

DANN

Benign

0.54

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.47

T;.

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.29

.;N

REVEL

Benign

0.048

Sift

Benign

0.16

.;T

Sift4G

Benign

0.37

T;T

Vest4

0.021

MutPred

0.16

Loss of ubiquitination at K1604 (P = 0.0825);Loss of ubiquitination at K1604 (P = 0.0825);

MPC

0.094

ClinPred

0.0059

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.10

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