rs2228220

Positions:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000379388.7(HIVEP1):c.3221A>G(p.Asn1074Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,994 control chromosomes in the GnomAD database, including 9,228 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.11 ( 1140 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8088 hom. )

Consequence

HIVEP1
ENST00000379388.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0240

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001280725).

BP6

Variant 6-12123016-A-G is Benign according to our data. Variant chr6-12123016-A-G is described in ClinVar as [Benign]. Clinvar id is 402936.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 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.3221A>G	p.Asn1074Ser	missense_variant	4/9	ENST00000379388.7	NP_002105.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIVEP1	ENST00000379388.7 linkuse as main transcript	c.3221A>G	p.Asn1074Ser	missense_variant	4/9	1	NM_002114.4	ENSP00000368698	P2	P15822-1
HIVEP1	ENST00000541134.5 linkuse as main transcript	c.3221A>G	p.Asn1074Ser	missense_variant	4/9	5		ENSP00000445617	A2
HIVEP1	ENST00000627968.2 linkuse as main transcript	c.-3083A>G		5_prime_UTR_variant	4/8	5		ENSP00000486543
HIVEP1	ENST00000442081.6 linkuse as main transcript	c.166+3082A>G		intron_variant		3		ENSP00000409078

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17415

AN:

152090

Hom.:

1133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.0944

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.0544

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0957

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.106

AC:

26502

AN:

249158

Hom.:

1623

AF XY:

0.110

AC XY:

14890

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.0664

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.0592

Gnomad NFE exome

AF:

0.0980

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.100

AC:

146625

AN:

1461786

Hom.:

8088

Cov.:

AF XY:

0.103

AC XY:

74817

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.0691

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.0596

Gnomad4 NFE exome

AF:

0.0945

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.115

AC:

17452

AN:

152208

Hom.:

1140

Cov.:

AF XY:

0.113

AC XY:

8437

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0942

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.0544

Gnomad4 NFE

AF:

0.0957

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.105

Hom.:

2358

Bravo

AF:

0.118

TwinsUK

AF:

0.0939

AC:

348

ALSPAC

AF:

0.0929

AC:

358

ESP6500AA

AF:

0.153

AC:

574

ESP6500EA

AF:

0.0885

AC:

725

ExAC

AF:

0.110

AC:

13237

Asia WGS

AF:

0.169

AC:

589

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 28, 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: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.40

DANN

Benign

0.26

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.61

T;.

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.53

.;N

REVEL

Benign

0.011

Sift

Benign

0.49

.;T

Sift4G

Benign

0.42

T;T

Vest4

0.010

MPC

0.069

ClinPred

0.0018

GERP RS

-0.52

gMVP

0.071

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